Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia

Background and Objective Altered levels of naturally occurring autoantibodies (nAbs) against disease-associated neuronal proteins have been reported for neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Recent histopathologic studies suggest a contribution of both Lewy body-and AD-related pathology to Parkinson's disease dementia (PDD). Therefore, we explored nAbs against alpha-synuclein (alpha S), tau and beta-amyloid (A beta) in PDD compared to cognitively normal PD patients. Materials and Methods We established three different ELISAs to quantify the nAbs-tau, nAbs-alpha S, and nAbs-A beta levels and avidity towards their specific antigen in serum samples of 18 non-demented (PDND) and 18 demented PD patients (PDD), which were taken from an ongoing multi-center cohort study (DEMPARK/LANDSCAPE). Results PDD patients had significantly decreased nAbs-tau serum levels compared to PDND patients (p = 0.007), whereas the serum titers of nAbs-alpha S and nAbs-A beta were unchanged. For all three nAbs, no significant differences in avidity were found between PDD and PDND cohorts. However, within both patient groups, nAbs-tau showed lowest avidity to their antigen, followed by nAbs-alpha S, and nAbs-A beta. Though, due to a high interassay coefficient of variability and the exclusion of many samples below the limit of detection, conclusions for nAbs-A beta are only conditionally possible. Conclusion We detected a significantly decreased nAbs-tau serum level in PDD patients, indicating a potential linkage between nAbs-tau serum titer and cognitive deficits in PD. Thus, further investigation in larger samples is justified to confirm our findings.