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

نویسندگان

  • Yannick Kronimus
  • Alexandra Albus
  • Monika Balzer-Geldsetzer
  • Sarah Straub
  • Elisa Semler
  • Markus Otto
  • Jens Klotsche
  • Richard Dodel
  • David Mengel
چکیده

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 (αS), tau and β-amyloid (Aβ) in PDD compared to cognitively normal PD patients. MATERIALS AND METHODS We established three different ELISAs to quantify the nAbs-tau, nAbs-αS, and nAbs-Aβ 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-αS and nAbs-Aβ 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-αS, and nAbs-Aβ. Though, due to a high interassay coefficient of variability and the exclusion of many samples below the limit of detection, conclusions for nAbs-Aβ 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Comparable Autoantibody Serum Levels against Amyloid- and Inflammation-Associated Proteins in Parkinson’s Disease Patients and Controls

Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD) and P...

متن کامل

Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements.

Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach for clearing pathological protein conformers in these disorders. This type of treatment has not been assessed in models that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer's disease. Here, we present that active immunization with a phosphorylated tau epitope...

متن کامل

Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (n = 12), Alzheimer's disease (n = 9), Parkinson's disease (n = 9), amyotrophic lateral sclerosis (...

متن کامل

Identification of the Sites of Tau Hyperphosphorylation and Activation of Tau Kinases in Synucleinopathies and Alzheimer’s Diseases

OBJECTIVE Most neurodegenerative diseases contain hyperphosphorylated Tau [p-Tau]. We examined for the first time epitopes at which Tau is hyperphosphorylated in Parkinson's disease, dementia with Lewy bodies and Alzheimer's disease, and also select Tau kinases. METHODS Postmortem frontal cortex from Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease and striata from Parkinso...

متن کامل

Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro

Objective(s):Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. One of the hallmarks of AD is an abnormal accumulation of fibril forms of tau protein which is known as a microtubule associated protein. In this regard, inhibition of tau aggregation has been documented to be a potent therapeutic approach in AD and tauopathies. Unfortunately, the available syntheti...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2016