Oligomeric α-synuclein and β-amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases
Oligomeric forms of α‐synuclein and β‐amyloid are toxic protein variants that are thought to contribute to the onset and progression of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. The detection of toxic variants in human cerebrospinal fluid (CSF) and blood has grea...
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Published in | The European journal of neuroscience Vol. 43; no. 1; pp. 3 - 16 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
France
Blackwell Publishing Ltd
01.01.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Oligomeric forms of α‐synuclein and β‐amyloid are toxic protein variants that are thought to contribute to the onset and progression of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. The detection of toxic variants in human cerebrospinal fluid (CSF) and blood has great promise for facilitating early and accurate diagnoses of these devastating diseases. Two hurdles that have impeded the use of these protein variants as biomarkers are the availability of reagents that can bind the different variants and a sensitive assay to detect their very low concentrations. We previously isolated antibody‐based reagents that selectively bind two different oligomeric variants of α‐synuclein and two of β‐amyloid, and developed a phage‐based capture enzyme‐linked immunosorbent assay (ELISA) with subfemtomolar sensitivity to quantify their presence. Here, we used these reagents to show that these oligomeric α‐synuclein variants are preferentially present in PD brain tissue, CSF and serum, and that the oligomeric β‐amyloid variants are preferentially present in AD brain tissue, CSF, and serum. Some AD samples also had α‐synuclein pathology and some PD samples also had β‐amyloid pathology, and, very intriguingly, these PD cases also had a history of dementia. Detection of different oligomeric α‐synuclein and β‐amyloid species is an effective method for identifying tissue, CSF and sera from PD and AD samples, respectively, and samples that also contained early stages of other protein pathologies, indicating their potential value as blood‐based biomarkers for neurodegenerative diseases.
Anti‐oligomeric alpha‐synuclein antibodies preferentially recognized PD cases, whereas anti‐oligomeric beta‐amyloid antibodies favored AD cases. Oligomeric protein variants were identified in human brain tissue, CSF and sera using the corresponding antibodies. Multiple protein pathologies were also detected in some cases. Recognition in sera indicates the sensitivity of our phage ELISA technology and its potential to simplify future diagnostic procedures. |
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Bibliography: | National Institute of Neurological Disorders and Stroke - No. U24 NS072026 National Institute on Aging - No. P30 AG19610 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders Michael J. Fox Foundation for Parkinson's Research Arizona Alzheimer's Research Center ArticleID:EJN13056 istex:D952F794DCA6F9978163CB3ECDD4A88BEB56998E Arizona Parkinson's Disease Consortium Arizona Alzheimer's Disease Core Center Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona ark:/67375/WNG-RQ2RH4RN-7 Arizona Department of Health Services - No. 211002 Banner Sun Health Research Institute - No. U24 NS072026; No. P30 AG19610; No. 211002; No. 4001; No. 0011; No. 05-901; No. 1001 DOD - No. U24 NS072026; No. P30 AG19610; No. 211002; No. 4001; No. 0011; No. 05-901; No. 1001 Fig. S1. Oligomeric α-synuclein or β-amyloid protein variants bound by scFvs. Fig. S2. 10H reactive oligomer levels in three ELISA trials utilizing brain tissue. Arizona Biomedical Research Commission - No. 4001; No. 0011; No. 05-901; No. 1001; No. W81XWH-12-1-0583 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0953-816X 1460-9568 |
DOI: | 10.1111/ejn.13056 |