[ { "key": "QTKD367A", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/QTKD367A", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/QTKD367A", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Rinne et al.", "parsedDate": "2010-04", "numChildren": 0 }, "data": { "key": "QTKD367A", "version": 1, "itemType": "journalArticle", "title": "11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study", "creators": [ { "creatorType": "author", "firstName": "Juha O", "lastName": "Rinne" }, { "creatorType": "author", "firstName": "David J", "lastName": "Brooks" }, { "creatorType": "author", "firstName": "Martin N", "lastName": "Rossor" }, { "creatorType": "author", "firstName": "Nick C", "lastName": "Fox" }, { "creatorType": "author", "firstName": "Roger", "lastName": "Bullock" }, { "creatorType": "author", "firstName": "William E", "lastName": "Klunk" }, { "creatorType": "author", "firstName": "Chester A", "lastName": "Mathis" }, { "creatorType": "author", "firstName": "Kaj", "lastName": "Blennow" }, { "creatorType": "author", "firstName": "Jerome", "lastName": "Barakos" }, { "creatorType": "author", "firstName": "Aren A", "lastName": "Okello" }, { "creatorType": "author", "firstName": "Sofia", "lastName": "Rodriguez Martinez de Liano" }, { "creatorType": "author", "firstName": "Enchi", "lastName": "Liu" }, { "creatorType": "author", "firstName": "Martin", "lastName": "Koller" }, { "creatorType": "author", "firstName": "Keith M", "lastName": "Gregg" }, { "creatorType": "author", "firstName": "Dale", "lastName": "Schenk" }, { "creatorType": "author", "firstName": "Ronald", "lastName": "Black" }, { "creatorType": "author", "firstName": "Michael", "lastName": "Grundman" } ], "abstractNote": "BACKGROUND: Carbon-11-labelled Pittsburgh compound B ((11)C-PiB) PET is a marker of cortical fibrillar amyloid-beta load in vivo. We used (11)C-PiB PET to investigate whether bapineuzumab, a humanised anti-amyloid-beta monoclonal antibody, would reduce cortical fibrillar amyloid-beta load in patients with Alzheimer's disease. METHODS: Patients with mild-to-moderate Alzheimer's disease were randomly assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to three in three ascending dose groups (0.5, 1.0, or 2.0 mg/kg). Each dose group was enrolled after safety review of the previous group. Randomisation was by interactive voice response system; masking was achieved with numbered kit allocation. Patients, investigators, study site personnel, sponsor staff, and carers were masked to treatment. Patients received up to six infusions, 13 weeks apart, and had (11)C-PiB PET scans at baseline and at weeks 20, 45, and 78. The primary outcome was the difference between the pooled bapineuzumab group and the pooled placebo group in mean change from screening to week 78 in (11)C-PiB cortical to cerebellar retention ratio averaged across six cortical regions of interest. Analysis was by modified intention to treat. This study is registered with EudraCT, number 2004-004120-12; ISRCTN17517446. FINDINGS: 28 patients were assigned to bapineuzumab (n=20) or placebo (n=8). 19 patients in the bapineuzumab group and seven in the placebo group were included in the modified intention-to-treat analysis. Estimated mean (11)C-PiB retention ratio change from baseline to week 78 was -0.09 (95% CI -0.16 to -0.02; p=0.014) in the bapineuzumab group and 0.15 (95% CI 0.02 to 0.28; p=0.022) in the placebo group. Estimated mean difference in (11)C-PiB retention ratio change from baseline to week 78 between the bapineuzumab group and the placebo group was -0.24 (95% CI -0.39 to -0.09; p=0.003). Differences between the bapineuzumab group and the placebo group in the individual regions of interest were similar to the overall mean difference. Adverse events were typically mild to moderate in severity and transient. Two patients in the 2.0 mg/kg bapineuzumab group had transient cerebral vasogenic oedema. INTERPRETATION: Treatment with bapineuzumab for 78 weeks reduced cortical (11)C-PiB retention compared with both baseline and placebo. (11)C-PiB PET seems to be useful in assessing the effects of potential Alzheimer's disease treatments on cortical fibrillar amyloid-beta load in vivo. FUNDING: Elan Pharmaceuticals and Wyeth Research.", "publicationTitle": "Lancet Neurology", "publisher": "", "place": "", "date": "Apr 2010", "volume": "9", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "363-372", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Lancet Neurol", "DOI": "10.1016/S1474-4422(10)70043-0", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/20189881", "accessDate": "2010-04-30T15:59:15Z", "PMID": "", "PMCID": "", "ISSN": "1474-4465", "archive": "", "archiveLocation": "", "shortTitle": "11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 20189881", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Amyloid beta-Protein", "type": 1 }, { "tag": "Aniline Compounds", "type": 1 }, { "tag": "Antibodies, Monoclonal", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "Brain Mapping", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Double-Blind Method", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Immunologic Factors", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Positron-Emission Tomography", "type": 1 }, { "tag": "Severity of Illness Index", "type": 1 }, { "tag": "Thiazoles", "type": 1 }, { "tag": "Time Factors", "type": 1 }, { "tag": "Treatment Outcome", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-05-02T18:32:51Z", "dateModified": "2010-05-02T18:32:51Z" } }, { "key": "V3NVEKDE", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/V3NVEKDE", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/V3NVEKDE", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Liu et al.", "parsedDate": "2009-09", "numChildren": 0 }, "data": { "key": "V3NVEKDE", "version": 1, "itemType": "journalArticle", "title": "Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles", "creators": [ { "creatorType": "author", "firstName": "Yang", "lastName": "Liu" }, { "creatorType": "author", "firstName": "Rongqin", "lastName": "Huang" }, { "creatorType": "author", "firstName": "Liang", "lastName": "Han" }, { "creatorType": "author", "firstName": "Weilun", "lastName": "Ke" }, { "creatorType": "author", "firstName": "Kun", "lastName": "Shao" }, { "creatorType": "author", "firstName": "Liya", "lastName": "Ye" }, { "creatorType": "author", "firstName": "Jinning", "lastName": "Lou" }, { "creatorType": "author", "firstName": "Chen", "lastName": "Jiang" } ], "abstractNote": "A 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) was exploited as a ligand for efficient brain-targeting gene delivery. RVG29 was modified on polyamidoamine dendrimers (PAMAM) through bifunctional PEG, then complexed with DNA, yielding PAMAM-PEG-RVG29/DNA nanoparticles (NPs). The NPs were observed to be uptaken by brain capillary endothelial cells (BCECs) through a clathrin and caveolae mediated energy-depending endocytosis. The specific cellular uptake can be inhibited by free RVG29 and GABA but not by nicotinic acetylcholine receptor (nAchR) agonists/antagonists, indicating RVG29 probably relates to the GABA(B) receptor besides nAchR reported previously. PAMAM-PEG-RVG29/DNA NPs showed higher blood-brain barrier (BBB)-crossing efficiency than PAMAM/DNA NPs in an in vitro BBB model. In vivo imaging showed that the NPs were preferably accumulated in brain. The report gene expression of the PAMAM-PEG-RVG29/DNA NPs was observed in brain, and significantly higher than unmodified NPs. Thus, PAMAM-PEG-RVG29 provides a safe and noninvasive approach for the gene delivery across the BBB.", "publicationTitle": "Biomaterials", "publisher": "", "place": "", "date": "Sep 2009", "volume": "30", "issue": "25", "section": "", "partNumber": "", "partTitle": "", "pages": "4195-4202", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biomaterials", "DOI": "10.1016/j.biomaterials.2009.02.051", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/19467700", "accessDate": "2010-04-30T15:48:43Z", "PMID": "", "PMCID": "", "ISSN": "1878-5905", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 19467700", "tags": [ { "tag": "Animals", "type": 1 }, { "tag": "Blood-Brain Barrier", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "Capillaries", "type": 1 }, { "tag": "Cells, Cultured", "type": 1 }, { "tag": "DNA, Viral", "type": 1 }, { "tag": "Drug Carriers", "type": 1 }, { "tag": "Endocytosis", "type": 1 }, { "tag": "Endothelial Cells", "type": 1 }, { "tag": "Gene Expression", "type": 1 }, { "tag": "Gene Therapy", "type": 1 }, { "tag": "Gene Transfer Techniques", "type": 1 }, { "tag": "Genetic Vectors", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Materials Testing", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Mice, Inbred BALB C", "type": 1 }, { "tag": "Mice, Nude", "type": 1 }, { "tag": "Nanoparticles", "type": 1 }, { "tag": "Polyamines", "type": 1 }, { "tag": "Rabies virus", "type": 1 }, { "tag": "Viral Envelope Proteins", "type": 1 }, { "tag": "gamma-Aminobutyric Acid", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-04-30T20:13:27Z", "dateModified": "2010-04-30T20:13:27Z" } }, { "key": "HTTXSR6U", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/HTTXSR6U", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/HTTXSR6U", "type": "text/html" } }, "meta": { "createdByUser": { "id": 138895, "username": "ked4p", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/ked4p", "type": "text/html" } } }, "creatorSummary": "Hebert et al.", "parsedDate": "2003-08", "numChildren": 0 }, "data": { "key": "HTTXSR6U", "version": 1, "itemType": "journalArticle", "title": "Alzheimer disease in the US population: prevalence estimates using the 2000 census", "creators": [ { "creatorType": "author", "firstName": "Liesi E", "lastName": "Hebert" }, { "creatorType": "author", "firstName": "Paul A", "lastName": "Scherr" }, { "creatorType": "author", "firstName": "Julia L", "lastName": "Bienias" }, { "creatorType": "author", "firstName": "David A", "lastName": "Bennett" }, { "creatorType": "author", "firstName": "Denis A", "lastName": "Evans" } ], "abstractNote": "CONTEXT: Current and future estimates of Alzheimer disease (AD) are essential for public health planning. OBJECTIVE: To provide prevalence estimates of AD for the US population from 2000 through 2050. DESIGN: Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. SETTING: A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. PARTICIPANTS: Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence. Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. RESULTS: In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. CONCLUSION: The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.", "publicationTitle": "Archives of Neurology", "publisher": "", "place": "", "date": "Aug 2003", "volume": "60", "issue": "8", "section": "", "partNumber": "", "partTitle": "", "pages": "1119-1122", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Arch. Neurol", "DOI": "10.1001/archneur.60.8.1119", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/12925369", "accessDate": "2010-03-02T00:14:32Z", "PMID": "", "PMCID": "", "ISSN": "0003-9942", "archive": "", "archiveLocation": "", "shortTitle": "Alzheimer disease in the US population", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 12925369", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Aged, 80 and over", "type": 1 }, { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Censuses", "type": 1 }, { "tag": "Cross-Sectional Studies", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Forecasting", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Neuropsychological Tests", "type": 1 }, { "tag": "Population Dynamics", "type": 1 }, { "tag": "Prevalence", "type": 1 }, { "tag": "United States", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-03-02T00:14:32Z", "dateModified": "2010-03-02T00:14:32Z" } }, { "key": "J98UCTCM", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/J98UCTCM", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/J98UCTCM", "type": "text/html" } }, "meta": { "createdByUser": { "id": 140839, "username": "law2yd", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/law2yd", "type": "text/html" } } }, "creatorSummary": "Montecucco", "parsedDate": "2001-10-01", "numChildren": 0 }, "data": { "key": "J98UCTCM", "version": 1, "itemType": "journalArticle", "title": "Detoxification of a bacterial toxin by the toxin itself", "creators": [ { "creatorType": "author", "firstName": "Cesare", "lastName": "Montecucco" } ], "abstractNote": "Several bacterial protein toxins act by forming oligomers on the cell surface. A novel approach to the prevention of the damage caused by oligomeric pore-forming toxins has recently been discovered using one such protein: the protective antigen (PA) of Bacillus anthracis. Some PA mutants act as dominant-negative effectors of the function performed by the oligomer. In fact, the PA mutant co-oligomerizes with native PA, but the mixed oligomer is non-functional. This finding might turn out to be of general validity.", "publicationTitle": "Trends in Pharmacological Sciences", "publisher": "", "place": "", "date": "October 1, 2001", "volume": "22", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "493-494", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1016/S0165-6147(00)01808-3", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/B6T1K-442RN26-2/2/72cdf3ace6c94c41c1a90ab44b4e1ccc", "accessDate": "2010-03-01T04:13:08Z", "PMID": "", "PMCID": "", "ISSN": "0165-6147", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T04:13:08Z", "dateModified": "2010-03-01T04:13:08Z" } }, { "key": "M94MUCDI", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/M94MUCDI", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/M94MUCDI", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/12085/items/K389GEGJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 140839, "username": "law2yd", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/law2yd", "type": "text/html" } } } }, "data": { "key": "M94MUCDI", "version": 1, "parentItem": "K389GEGJ", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed Central Link", "accessDate": "2010-03-01T03:47:40Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850152/", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2010-03-01T03:47:40Z", "dateModified": "2010-03-01T03:47:40Z" } }, { "key": "K389GEGJ", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/K389GEGJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/K389GEGJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 140839, "username": "law2yd", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/law2yd", "type": "text/html" } } }, "creatorSummary": "Hrncic et al.", "parsedDate": "2000-10", "numChildren": 1 }, "data": { "key": "K389GEGJ", "version": 1, "itemType": "journalArticle", "title": "Antibody-Mediated Resolution of Light Chain-Associated Amyloid Deposits", "creators": [ { "creatorType": "author", "firstName": "Rudi", "lastName": "Hrncic" }, { "creatorType": "author", "firstName": "Jonathan", "lastName": "Wall" }, { "creatorType": "author", "firstName": "Dennis A.", "lastName": "Wolfenbarger" }, { "creatorType": "author", "firstName": "Charles L.", "lastName": "Murphy" }, { "creatorType": "author", "firstName": "Maria", "lastName": "Schell" }, { "creatorType": "author", "firstName": "Deborah T.", "lastName": "Weiss" }, { "creatorType": "author", "firstName": "Alan", "lastName": "Solomon" } ], "abstractNote": "Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the VL or CL isotype of the fibril, but rather seemed to be directed toward a β-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. 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The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.", "publicationTitle": "The American Journal of Pathology", "publisher": "", "place": "", "date": "Oct 2000", "volume": "157", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1239-1246", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Am. J. Pathol", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/11021828", "accessDate": "2010-03-01T03:17:53Z", "PMID": "", "PMCID": "", "ISSN": "0002-9440", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 11021828", "tags": [ { "tag": "Amyloid", "type": 1 }, { "tag": "Amyloidosis", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Antibodies, Monoclonal", "type": 1 }, { "tag": "Epitopes", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Mice, Inbred BALB C", "type": 1 }, { "tag": "Molecular Conformation", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-03-01T03:17:53Z", "dateModified": "2010-03-01T03:17:53Z" } }, { "key": "22RMW8HK", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/22RMW8HK", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/22RMW8HK", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Zlokovic", "parsedDate": "2004-05", "numChildren": 0 }, "data": { "key": "22RMW8HK", "version": 1, "itemType": "journalArticle", "title": "Clearing amyloid through the blood-brain barrier", "creators": [ { "creatorType": "author", "firstName": "Berislav V", "lastName": "Zlokovic" } ], "abstractNote": "According to the amyloid hypothesis, accumulation of amyloid beta-peptide (A beta) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that A beta within the intravascular space is linked to A beta deposited in the brain suggesting that transport of A beta between the brain, blood and cerebrospinal fluid, and across the blood-brain barrier, regulates brain A beta. Thus, understanding A beta exchanges between brain and blood, and vice versa, and developing transport-based systemic A beta-lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD.", "publicationTitle": "Journal of Neurochemistry", "publisher": "", "place": "", "date": "May 2004", "volume": "89", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "807-811", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Neurochem", "DOI": "10.1111/j.1471-4159.2004.02385.x", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/15140180", "accessDate": "2010-02-28T00:42:30Z", "PMID": "", "PMCID": "", "ISSN": "0022-3042", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15140180", "tags": [ { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Amyloid beta-Protein", "type": 1 }, { "tag": "Blood-Brain Barrier", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "LDL-Receptor Related Proteins", "type": 1 }, { "tag": "Receptors, Immunologic", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:01:31Z", "dateModified": "2010-03-01T02:01:31Z" } }, { "key": "PQQ46TBI", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/PQQ46TBI", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/PQQ46TBI", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/12085/items/RRMU8TH4", "type": "application/json" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "PQQ46TBI", "version": 1, "parentItem": "RRMU8TH4", "itemType": "note", "note": "PMID: 10460176", "tags": [], "relations": {}, "dateAdded": "2010-03-01T02:01:24Z", "dateModified": "2010-03-01T02:01:24Z" } }, { "key": "RRMU8TH4", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/RRMU8TH4", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/RRMU8TH4", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Lin et al.", "parsedDate": "1999", "numChildren": 1 }, "data": { "key": "RRMU8TH4", "version": 1, "itemType": "journalArticle", "title": "Amyloid β Protein (1−40) Forms Calcium-Permeable, Zn2+-Sensitive Channel in Reconstituted Lipid Vesicles†,‡", "creators": [ { "creatorType": "author", "firstName": "Hai", "lastName": "Lin" }, { "creatorType": "author", "firstName": "Yinwen Judy", "lastName": "Zhu" }, { "creatorType": "author", "firstName": "Ratneshwar", "lastName": "Lal" } ], "abstractNote": "Amyloid beta protein (AbetaP) forms senile plaques in the cerebrocortical blood vessels and brain parenchyma of patients with Alzheimer's disease (AD). The nonfamilial or sporadic AD (SAD), the most prevalent form of AD, has been correlated with an increased level of 40-residue AbetaP (AbetaP1-40). However, very little is known about the role of AbetaP1-40 in AD pathophysiology. We have examined the activity of AbetaP1-40 reconstituted in phospholipid vesicles. A combined light fluorescence and atomic force microscope (AFM) was used to image the structure of reconstituted vesicles and 45Ca2+ uptake was used as an assay for calcium permeability across the vesicular membrane. Vesicles reconstituted with fresh and globular AbetaP1-40 contain a significant amount of AbetaP and exhibit strong immunofluorescence labeling with an antibody raised against the N-terminal domain of AbetaP, suggesting the incorporation of AbetaP1-40 peptide in the vesicular membrane. Vesicles reconstituted with AbetaP1-40 exhibited a significant level of 45Ca2+ uptake. The vesicular calcium level saturated over time, showing an important ion channel characteristic. The 45Ca2+ uptake was inhibited by (i) a monoclonal antibody raised against the N-terminal region of AbetaP and (ii) Zn2+. However, a reducing agent (DTT) did not inhibit the 45Ca2+ uptake, indicating that the oxidation of AbetaP or its surrounding lipid molecules is not directly involved in AbetaP-mediated Ca2+ uptake. These findings provide biochemical and structural evidence that fresh and globular AbetaP1-40 forms calcium-permeable channels and thus may induce cellular toxicity by regulating the calcium homeostasis in nonfamilial or sporadic Alzheimer's disease.", "publicationTitle": "Biochemistry", "publisher": "", "place": "", "date": "1999", "volume": "38", "issue": "34", "section": "", "partNumber": "", "partTitle": "", "pages": "11189-11196", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1021/bi982997c", "citationKey": "", "url": "http://dx.doi.org/10.1021/bi982997c", "accessDate": "2010-02-28T00:41:30Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ACS Publications", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:01:24Z", "dateModified": "2010-03-01T02:01:24Z" } }, { "key": "RPTX9JFH", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/RPTX9JFH", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/RPTX9JFH", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Shibata et al.", "parsedDate": "2000", "numChildren": 0 }, "data": { "key": "RPTX9JFH", "version": 1, "itemType": "journalArticle", "title": "Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier", "creators": [ { "creatorType": "author", "firstName": "Masayoshi", "lastName": "Shibata" }, { "creatorType": "author", "firstName": "Shinya", "lastName": "Yamada" }, { "creatorType": "author", "firstName": "S. Ram", "lastName": "Kumar" }, { "creatorType": "author", "firstName": "Miguel", "lastName": "Calero" }, { "creatorType": "author", "firstName": "James", "lastName": "Bading" }, { "creatorType": "author", "firstName": "Blas", "lastName": "Frangione" }, { "creatorType": "author", "firstName": "David M.", "lastName": "Holtzman" }, { "creatorType": "author", "firstName": "Carol A.", "lastName": "Miller" }, { "creatorType": "author", "firstName": "Dudley K.", "lastName": "Strickland" }, { "creatorType": "author", "firstName": "Jorge", "lastName": "Ghiso" }, { "creatorType": "author", "firstName": "Berislav V.", "lastName": "Zlokovic" } ], "abstractNote": "", "publicationTitle": "Journal of Clinical Investigation", "publisher": "", "place": "", "date": "12/2000", "volume": "106", "issue": "12", "section": "", "partNumber": "", "partTitle": "", "pages": "1489-1499", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Clin. Invest.", "DOI": "10.1172/JCI10498", "citationKey": "", "url": "http://www.jci.org/articles/view/10498", "accessDate": "2010-02-28T01:15:03Z", "PMID": "", "PMCID": "", "ISSN": "0021-9738", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "CrossRef", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:01:12Z", "dateModified": "2010-03-01T02:01:12Z" } }, { "key": "KTUKRF3N", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/KTUKRF3N", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/KTUKRF3N", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Cohen et al.", "parsedDate": "2009-09", "numChildren": 0 }, "data": { "key": "KTUKRF3N", "version": 1, "itemType": "journalArticle", "title": "Anti-Amyloid Effects of Small Molecule Abeta-Binding Agents in PS1/APP Mice", "creators": [ { "creatorType": "author", "firstName": "A D", "lastName": "Cohen" }, { "creatorType": "author", "firstName": "M D", "lastName": "Ikonomovic" }, { "creatorType": "author", "firstName": "E E", "lastName": "Abrahamson" }, { "creatorType": "author", "firstName": "W R", "lastName": "Paljug" }, { "creatorType": "author", "firstName": "S T", "lastName": "Dekosky" }, { "creatorType": "author", "firstName": "I M", "lastName": "Lefterov" }, { "creatorType": "author", "firstName": "R P", "lastName": "Koldamova" }, { "creatorType": "author", "firstName": "L", "lastName": "Shao" }, { "creatorType": "author", "firstName": "M L", "lastName": "Debnath" }, { "creatorType": "author", "firstName": "N S", "lastName": "Mason" }, { "creatorType": "author", "firstName": "C A", "lastName": "Mathis" }, { "creatorType": "author", "firstName": "W E", "lastName": "Klunk" } ], "abstractNote": "AIMS: One promising approach for treatment of Alzheimer's disease (AD) is use of anti-amyloid therapies, based on the hypothesis that increases in amyloid-beta (Abeta) deposits in brain are a major cause of AD. Several groups have focused on Abeta immunotherapy with some success. Small molecules derivatives of Congo red have been shown to inhibit Abeta aggregation and protect against Abeta neurotoxicity in vitro. The agents described here are all small molecule Abeta-binding agents (SMAbetaBA's) derivatives of Congo red. MAIN METHODS: Here, we have explored the anti-amyloid properties of these SMAbetaBA's in mice doubly transgenic for human prensenilin-1 (PS1) and APP gene mutations that cause early-onset AD. Mice were treated with either methoxy-X04, X:EE:B34 and X:034-3-OMe1. After treatment, brains were examined for Abeta-deposition, using histochemistry, and soluble and insoluble Abeta levels were determined using ELISA. KEY FINDINGS: A range of anti-amyloid activity was observed with these three compounds. PS1/APP mice treated with methoxy-X04 and X:EE:B34 showed decrease in total Abeta load, a decrease in Abeta fibril load, and a decrease in average plaque size. Treatment with methoxy-X04 also resulted in a decrease in insoluble Abeta levels. The structurally similar compound, X:034:3-OMe1, showed no significant effect on any of these measures. The effectiveness of the SMAbetaBA's may be related to a combination of binding affinity for Abeta and entry into brain, but other factors appear to apply as well. SIGNIFICANCE: These data suggest that SMAbetaBA's may significantly decrease amyloid burden in brain during the pathogenesis of AD and could be useful therapeutics alone, or in combination with immunotherapy.", "publicationTitle": "Letters in Drug Design & Discovery", "publisher": "", "place": "", "date": "Sep 2009", "volume": "6", "issue": "6", "section": "", "partNumber": "", "partTitle": "", "pages": "437", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Lett Drug Des Discov", "DOI": "10.2174/157018009789057526", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/20119496", "accessDate": "2010-02-21T05:10:56Z", "PMID": "", "PMCID": "", "ISSN": "1570-1808", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 20119496", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:01:00Z", "dateModified": "2010-03-01T02:01:00Z" } }, { "key": "IIVNQV3C", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/IIVNQV3C", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/IIVNQV3C", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Naslund et al.", "parsedDate": "2000-03-22", "numChildren": 0 }, "data": { "key": "IIVNQV3C", "version": 1, "itemType": "journalArticle", "title": "Correlation Between Elevated Levels of Amyloid {beta}-Peptide in the Brain and Cognitive Decline", "creators": [ { "creatorType": "author", "firstName": "Jan", "lastName": "Naslund" }, { "creatorType": "author", "firstName": "Vahram", "lastName": "Haroutunian" }, { "creatorType": "author", "firstName": "Richard", "lastName": "Mohs" }, { "creatorType": "author", "firstName": "Kenneth L.", "lastName": "Davis" }, { "creatorType": "author", "firstName": "Peter", "lastName": "Davies" }, { "creatorType": "author", "firstName": "Paul", "lastName": "Greengard" }, { "creatorType": "author", "firstName": "Joseph D.", "lastName": "Buxbaum" } ], "abstractNote": "Context Alzheimer disease (AD) is characterized neuropathologically by the presence of amyloid {beta}-peptide (A{beta})-containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of A{beta} correlates with dementia and whether A{beta} alterations precede or follow changes in tau. Objectives To determine whether accumulation of A{beta} correlates with the earliest signs of cognitive deterioration and to define the relationship between A{beta} accumulation and early tau changes. Design, Setting, and Patients Postmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of A{beta} variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia. Main Outcome Measures Levels of total A{beta} peptides with intact or truncated amino termini and ending in either amino acid 40 (A{beta}x-40) or 42 (A{beta}x-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score. Results The levels of both A{beta}x-40 and A{beta}x-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone A{beta}x-42 peptide were higher than those of A{beta}x-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in A{beta}x-40 and A{beta}x-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease. Conclusions In this study, levels of total A{beta}x-40 and A{beta}x-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, A{beta} was elevated before the occurrence of significant tau pathology. These results support an important role for A{beta} in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of A{beta} should be pursued.", "publicationTitle": "JAMA", "publisher": "", "place": "", "date": "March 22, 2000", "volume": "283", "issue": "12", "section": "", "partNumber": "", "partTitle": "", "pages": "1571-1577", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1001/jama.283.12.1571", "citationKey": "", "url": "http://jama.ama-assn.org/cgi/content/abstract/283/12/1571", "accessDate": "2010-02-28T15:03:33Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "HighWire", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:00:52Z", "dateModified": "2010-03-01T02:00:52Z" } }, { "key": "7TTN8BMJ", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/7TTN8BMJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/7TTN8BMJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Paravastu et al.", "parsedDate": "2009-05-05", "numChildren": 0 }, "data": { "key": "7TTN8BMJ", "version": 1, "itemType": "journalArticle", "title": "Seeded growth of β-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure", "creators": [ { "creatorType": "author", "firstName": "Anant K.", "lastName": "Paravastu" }, { "creatorType": "author", "firstName": "Isam", "lastName": "Qahwash" }, { "creatorType": "author", "firstName": "Richard D.", "lastName": "Leapman" }, { "creatorType": "author", "firstName": "Stephen C.", "lastName": "Meredith" }, { "creatorType": "author", "firstName": "Robert", "lastName": "Tycko" } ], "abstractNote": "Studies by solid-state nuclear magnetic resonance (NMR) of amyloid fibrils prepared from synthetic 40-residue β-amyloid (Aβ) peptides have shown that the molecular structure of Aβ fibrils is not uniquely determined by amino acid sequence. Instead, the fibril structure depends on the precise details of growth conditions. The molecular structures of β-amyloid fibrils that develop in Alzheimer's disease (AD) are therefore uncertain. We demonstrate through thioflavin T fluorescence and electron microscopy that fibrils extracted from brain tissue of deceased AD patients can be used to seed the growth of synthetic Aβ fibrils, allowing preparation of fibrils with isotopic labeling and in sufficient quantities for solid-state NMR and other measurements. Because amyloid structures propagate themselves in seeded growth, as shown in previous studies, the molecular structures of brain-seeded synthetic Aβ fibrils most likely reflect structures that are present in AD brain. Solid-state C NMR spectra of fibril samples seeded with brain material from two AD patients were found to be nearly identical, indicating the same molecular structures. Spectra of an unseeded control sample indicate greater structural heterogeneity. C chemical shifts and other NMR data indicate that the predominant molecular structure in brain-seeded fibrils differs from the structures of purely synthetic Aβ fibrils that have been characterized in detail previously. These results demonstrate a new approach to detailed structural characterization of amyloid fibrils that develop in human tissue, and to investigations of possible correlations between fibril structure and the degree of cognitive impairment and neurodegeneration in AD.", "publicationTitle": "Proceedings of the National Academy of Sciences", "publisher": "", "place": "", "date": "May 05, 2009", "volume": "106", "issue": "18", "section": "", "partNumber": "", "partTitle": "", "pages": "7443-7448", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1073/pnas.0812033106", "citationKey": "", "url": "http://www.pnas.org/content/106/18/7443.abstract", "accessDate": "2010-02-21T01:34:00Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "Highwire 2.0", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:00:40Z", "dateModified": "2010-03-01T02:00:40Z" } }, { "key": "ST57HDD2", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/ST57HDD2", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/ST57HDD2", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Soto and Estrada", "parsedDate": "2008-02-01", "numChildren": 0 }, "data": { "key": "ST57HDD2", "version": 1, "itemType": "journalArticle", "title": "Protein Misfolding and Neurodegeneration", "creators": [ { "creatorType": "author", "firstName": "Claudio", "lastName": "Soto" }, { "creatorType": "author", "firstName": "Lisbell D.", "lastName": "Estrada" } ], "abstractNote": "A key molecular pathway implicated in diverse neurodegenerative diseases is the misfolding, aggregation, and accumulation of proteins in the brain. Compelling evidence strongly supports the hypothesis that accumulation of misfolded proteins leads to synaptic dysfunction, neuronal apoptosis, brain damage, and disease. However, the mechanism by which protein misfolding and aggregation trigger neurodegeneration and the identity of the neurotoxic structure is still unclear. The aim of this article is to review the literature around the molecular mechanism and role of misfolded protein aggregates in neurodegeneration and the potential for the misfolding process to lead to a transmissible form of disease by a prion-based model of propagation.", "publicationTitle": "Arch Neurol", "publisher": "", "place": "", "date": "February 1, 2008", "volume": "65", "issue": "2", "section": "", "partNumber": "", "partTitle": "", "pages": "184-189", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1001/archneurol.2007.56", "citationKey": "", "url": "http://archneur.ama-assn.org/cgi/content/abstract/65/2/184", "accessDate": "2010-02-20T18:11:32Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "HighWire", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:00:29Z", "dateModified": "2010-03-01T02:00:29Z" } }, { "key": "V4GCR983", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/V4GCR983", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/V4GCR983", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Weller et al.", "parsedDate": "2009-07", "numChildren": 0 }, "data": { "key": "V4GCR983", "version": 1, "itemType": "journalArticle", "title": "Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy", "creators": [ { "creatorType": "author", "firstName": "Roy O", "lastName": "Weller" }, { "creatorType": "author", "firstName": "Delphine", "lastName": "Boche" }, { "creatorType": "author", "firstName": "James A R", "lastName": "Nicoll" } ], "abstractNote": "The introduction of immunotherapy and its ultimate success will require re-evaluation of the pathogenesis of Alzheimer's disease particularly with regard to the role of the ageing microvasculature and the effects of APOE genotype. Arteries in the brain have two major functions (a) delivery of blood and (b) elimination of interstitial fluid and solutes, including amyloid-beta (Abeta), along perivascular pathways (lymphatic drainage). Both these functions fail with age and particularly severely in Alzheimer's disease and vascular dementia. Accumulation of Abeta as plaques in brain parenchyma and artery walls as cerebral amyloid angiopathy (CAA) is associated with failure of perivascular elimination of Abeta from the brain in the elderly and in Alzheimer's disease. High levels of soluble Abeta in the brain correlate with cognitive decline in Alzheimer's disease and reflect the failure of perivascular drainage of solutes from the brain and loss of homeostasis of the neuronal environment. Clinically and pathologically, there is a spectrum of disease related to functional failure of the ageing microvasculature with \"pure\" Alzheimer's disease at one end of the spectrum and vascular dementia at the other end. Changes in the cerebral microvasculature with age have a potential impact on therapy with cholinesterase inhibitors and especially on immunotherapy that removes Abeta from plaques in the brain, but results in an increase in severity of CAA and no clear improvement in cognition. Drainage of Abeta along perivascular pathways in ageing artery walls may need to be improved to maximise the potential for improvement of cognitive function with immunotherapy.", "publicationTitle": "Acta Neuropathologica", "publisher": "", "place": "", "date": "Jul 2009", "volume": "118", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "87-102", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Acta Neuropathol", "DOI": "10.1007/s00401-009-0498-z", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/19234858", "accessDate": "2010-02-20T19:27:54Z", "PMID": "", "PMCID": "", "ISSN": "1432-0533", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 19234858", "tags": [ { "tag": "Aging", "type": 1 }, { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Amyloid beta-Protein", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "Cerebral Amyloid Angiopathy", "type": 1 }, { "tag": "Cholinesterase Inhibitors", "type": 1 }, { "tag": "Dementia, Vascular", "type": 1 }, { "tag": "Microvessels", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:00:14Z", "dateModified": "2010-03-01T02:00:14Z" } }, { "key": "R9MAD6TT", "version": 1, "library": { "type": "group", "id": 12085, "name": "BME 2104 Amyloidosis Research Paper", "links": { "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/12085/items/R9MAD6TT", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/bme_2104_amyloidosis_research_paper/items/R9MAD6TT", "type": "text/html" } }, "meta": { "createdByUser": { "id": 141429, "username": "juliekok", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/juliekok", "type": "text/html" } } }, "creatorSummary": "Schenk et al.", "parsedDate": "1999-07-08", "numChildren": 0 }, "data": { "key": "R9MAD6TT", "version": 1, "itemType": "journalArticle", "title": "Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse", "creators": [ { "creatorType": "author", "firstName": "D", "lastName": "Schenk" }, { "creatorType": "author", "firstName": "R", "lastName": "Barbour" }, { "creatorType": "author", "firstName": "W", "lastName": "Dunn" }, { "creatorType": "author", "firstName": "G", "lastName": "Gordon" }, { "creatorType": "author", "firstName": "H", "lastName": "Grajeda" }, { "creatorType": "author", "firstName": "T", "lastName": "Guido" }, { "creatorType": "author", "firstName": "K", "lastName": "Hu" }, { "creatorType": "author", "firstName": "J", "lastName": "Huang" }, { "creatorType": "author", "firstName": "K", "lastName": "Johnson-Wood" }, { "creatorType": "author", "firstName": "K", "lastName": "Khan" }, { "creatorType": "author", "firstName": "D", "lastName": "Kholodenko" }, { "creatorType": "author", "firstName": "M", "lastName": "Lee" }, { "creatorType": "author", "firstName": "Z", "lastName": "Liao" }, { "creatorType": "author", "firstName": "I", "lastName": "Lieberburg" }, { "creatorType": "author", "firstName": "R", "lastName": "Motter" }, { "creatorType": "author", "firstName": "L", "lastName": "Mutter" }, { "creatorType": "author", "firstName": "F", "lastName": "Soriano" }, { "creatorType": "author", "firstName": "G", "lastName": "Shopp" }, { "creatorType": "author", "firstName": "N", "lastName": "Vasquez" }, { "creatorType": "author", "firstName": "C", "lastName": "Vandevert" }, { "creatorType": "author", "firstName": "S", "lastName": "Walker" }, { "creatorType": "author", "firstName": "M", "lastName": "Wogulis" }, { "creatorType": "author", "firstName": "T", "lastName": "Yednock" }, { "creatorType": "author", "firstName": "D", "lastName": "Games" }, { "creatorType": "author", "firstName": "P", "lastName": "Seubert" } ], "abstractNote": "Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.", "publicationTitle": "Nature", "publisher": "", "place": "", "date": "Jul 8, 1999", "volume": "400", "issue": "6740", "section": "", "partNumber": "", "partTitle": "", "pages": "173-177", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Nature", "DOI": "10.1038/22124", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/10408445", "accessDate": "2010-02-21T03:36:21Z", "PMID": "", "PMCID": "", "ISSN": "0028-0836", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 10408445", "tags": [ { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Amyloid beta-Protein", "type": 1 }, { "tag": "Astrocytes", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "Buffers", "type": 1 }, { "tag": "Enzyme-Linked Immunosorbent Assay", "type": 1 }, { "tag": "Freund's Adjuvant", "type": 1 }, { "tag": "Hippocampus", "type": 1 }, { "tag": "Mice, Transgenic", "type": 1 }, { "tag": "Neurites", "type": 1 }, { "tag": "Peptide Fragments", "type": 1 }, { "tag": "Point Mutation", "type": 1 }, { "tag": "Serum Amyloid P-Component", "type": 1 }, { "tag": "Vaccination", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2010-03-01T02:00:08Z", "dateModified": "2010-03-01T02:00:08Z" } } ]