title: Antiphospholipid autoantibodies as blood biomarkers for detection of early stage Alzheimer's disease.
abstract: A robust blood biomarker is urgently needed to facilitate early prognosis for those at risk for Alzheimer's disease (AD). Redox reactive autoantibodies (R-RAAs) represent a novel family of antibodies detectable only after exposure of cerebrospinal fluid (CSF), serum, plasma or immunoglobulin fractions to oxidizing agents. We have previously reported that R-RAA antiphospholipid antibodies (aPLs) are significantly decreased in the CSF and serum of AD patients compared to healthy controls (HCs). These studies were extended to measure R-RAA aPL in serum samples obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI). Serum samples from the ADNI-1 diagnostic groups from participants with mild cognitive impairment (MCI), AD and HCs were blinded for diagnosis and analyzed for R-RAA aPL by ELISA. Demographics, cognitive data at baseline and yearly follow-up were subsequently provided by ADNI after posting assay data. As observed in CSF, R-RAA aPL in sera from the AD diagnostic group were significantly reduced compared to HC. However, the sera from the MCI population contained significantly elevated R-RAA aPL activity relative to AD patient and/or HC sera. The data presented in this study indicate that R-RAA aPL show promise as a blood biomarker for detection of early AD, and warrant replication in a larger sample. Longitudinal testing of an individual for increases in R-RAA aPL over a previously established baseline may serve as a useful early sero-epidemiologic blood biomarker for individuals at risk for developing dementia of the Alzheimer's type.
authors: HLA-Vascular Biology Laboratory, Franciscan St. Francis Health , Indianapolis, IN , USA .
authors: John A
authors: JA
authors: McIntyre
authors: Curtis J
authors: CJ
authors: Ramsey
authors: Bruce D
authors: BD
authors: Gitter
authors: Andrew J
authors: AJ
authors: Saykin
authors: Dawn R
authors: DR
authors: Wagenknecht
authors: Paul A
authors: PA
authors: Hyslop
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000097:blood* / Q000276:immunology; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D007074:Immunoglobulin G
keywords: ELISA; mild cognitive impairment; neurodegenerative disease; redox-reactive antiphospholipid autoantibodies; serum biomarkers