Dataset Information

Elevated Serum ?-Synuclein Autoantibodies in Patients with Parkinson's Disease Relative to Alzheimer's Disease and Controls.

ABSTRACT: Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson's disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against ?-synuclein (?-syn), which is an important protein involved in the pathogenesis of PD. In our study patients with PD (46 patients), Alzheimer's disease (AD) (27 patients) and healthy controls (20 patients) were evaluated according to their sera ?-syn AIAs levels. Interestingly, ?-syn AIAs were significantly elevated in PD group compared to AD and healthy controls, which advocates their use for diagnosis of PD.

SUBMITTER: Shalash A

PROVIDER: S-EPMC5744443 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson's Disease Relative to Alzheimer's Disease and Controls.

Shalash Ali A Salama Mohamed M Makar Marianne M Roushdy Tamer T Elrassas Hanan Hany HH Mohamed Wael W El-Balkimy Mahmoud M Abou Donia Mohamed M

Frontiers in neurology 20171222

Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson's disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against α-synuclein ...[more]

PMID: 29312137

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Project description:BACKGROUND:Neurofilament light chain is a marker of axonal damage and is of interest as a biofluid biomarker for PD. The objective of this study was to investigate whether CSF or serum neurofilament contributes to a combination of CSF biomarkers in defining the optimal biomarker panel for discriminating PD patients from healthy controls. In addition, we aimed to assess whether CSF and/or serum neurofilament levels are associated with clinical measures of disease severity. METHODS:We measured neurofilament light chain levels in CSF and/or serum of 139 PD patients and 52 age-matched healthy controls. We used stepwise logistic regression analyses to test whether neurofilament contributes to a biomarker CSF panel including total, oligomeric, and phosphorylated ?-synuclein and Alzheimer's disease biomarkers. Measures of disease severity included disease duration, UPDRS-III, Hoehn & Yahr stage, and MMSE. RESULTS:After correcting for age, CSF neurofilament levels were 42% higher in PD patients compared with controls (P?<?0.01), whereas serum neurofilament levels were 37% higher (P = 0.08). Combining CSF neurofilament, phosphorylated-/total ?-synuclein, and oligomeric-/total ?-synuclein yielded the best-fitting model for discriminating PD patients from controls (area under the curve 0.92). The discriminatory potential of serum neurofilament in the CSF biomarker panel was similar (area under the curve 0.90). Higher serum neurofilament was associated with a lower MMSE score. There were no other associations between CSF and/or serum neurofilament levels and clinical disease severity. CONCLUSIONS:CSF neurofilament contributes to a panel of CSF ?-synuclein species in differentiating PD patients from healthy controls. Serum neurofilament may have added value to a biofluid biomarker panel for differentiating PD patients from controls. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Project description:Background: Recent efforts have described an immunogenic component to the pathobiology of Alzheimer's disease (AD) and Parkinson's disease (PD). However, current methods of studying fluid autoantibodies, such as enzyme-linked immunosorbent assays and immunohistochemistry, are hypothesis-driven and not optimal for discovering new autoantibody biomarkers by proteome-wide screening. Recently, we developed a general mass spectrometry-based approach to identify tissue-specific autoantibodies in serum, at a proteome-wide level. In this study, we adapted the method to explore novel autoantibody biomarkers in the cerebrospinal fluid (CSF) of AD and PD patients. Methods: CSF samples were obtained from 10 headache control individuals, 10 AD patients and 10 PD patients. Antibodies present in the CSF were isolated by immobilization to protein-G magnetic beads. These antibodies were incubated with a brain tissue extract, prepared from frontal cortex, pons, cerebellum and brain stem. Protein antigens captured by the protein-G magnetic bead-bound antibodies were digested with trypsin and analyzed using mass spectrometry. Autoantibody candidates were selected by 1) detection in one or less individuals of the control group and 2) identification in at least half of the patient groups. Results: There were 16 putative autoantibody biomarkers selected from the AD group. Glia-derived nexin autoantibody was detected in eight of ten AD patients and was absent in the control group. Other AD pathology-related targets were also identified, such as actin-interaction protein, quinone oxidoreductase, sushi repeat-containing protein, metalloproteinase inhibitor 2, IP3 receptor 1 and sarcoplasmic/endoplasmic reticulum calcium ATPase 2. An additional eleven autoantibody targets were also identified in the present experiment, although their link to AD is not clear. No autoantibodies in the PD group satisfied our selection criteria. Conclusion: Our unbiased mass spectrometry method was able to detect new putative CSF autoantibody biomarkers of AD. Further investigation into the involvement of humoral autoimmunity in AD and PD pathobiology may be warranted.

Dataset Information

Elevated Serum ?-Synuclein Autoantibodies in Patients with Parkinson's Disease Relative to Alzheimer's Disease and Controls.

Publications

Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson's Disease Relative to Alzheimer's Disease and Controls.

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