Abstract
Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against α-synuclein is not well known. We explored serum IgG levels to monomeric α-synuclein in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-α-synuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against α-synuclein in DLB and AD, which may relate to a disturbed α-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target α-synuclein in neurodegenerative disease.
Highlights
Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most frequent forms of dementia and belong to the tauopathies and synucleinopathies, respectively
Healthy control individuals were recruited from healthy spouses or volunteers that did not complain of any cognitive problems, and who were unremarkable in cognition and cognitive flexibility
Measurement of Anti-a-synuclein IgG The ELISA was extensively tested with various modifications to achieve utmost specificity and reliability
Summary
Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most frequent forms of dementia and belong to the tauopathies and synucleinopathies, respectively. Clinical diagnosis and distinction of the disorders are often difficult especially at very early and late stages of disease, with a definite diagnosis usually only being made upon autopsy. Despite the revised clinical guidelines, the consensus criteria for the diagnosis of DLB [1] is frequently lacking sensitivity, especially at disease onset [2]. In AD, Lewy bodies and Lewy neurites are frequently observed [4], and DLB often meets the histological criteria of AD [1]. Early, preferably preclinical diagnosis of an evolving dementia and a better diagnostic distinction of DLB versus AD is an important goal. To meet this challenge, the development of sensitive and specific biomarkers is crucial
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