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 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.
Chemical Engineering, The School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287-6106, USA.
Stephanie M
SM
Williams
Chemical Engineering, The School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287-6106, USA.
Philip
P
Schulz
Chemical Engineering, The School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287-6106, USA.
Michael R
MR
Sierks
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D012680:Sensitivity and Specificity; D013702:Temporal Lobe / Q000378:metabolism; D051844:alpha-Synuclein / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D051844:alpha-Synuclein
brain tissue; cerebrospinal fluid; phage capture enzyme-linked immunosorbent assay; serum; single-chain variable fragments