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P2‐044: Oxidized Pin1 and alpha‐synuclein in the cerebrospinal fluid as putative biomarkers for Alzheimer's and Parkinson's diseases
Author(s) -
Bochem MarieChristine,
Herbert Megan,
Kuiperij H. Bea,
Verbeek Marcel M.
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.747
Subject(s) - pin1 , cerebrospinal fluid , oxidative stress , alpha synuclein , recombinant dna , chemistry , parkinson's disease , antibody , peptidylprolyl isomerase , amyloid (mycology) , disease , biomarker , biochemistry , medicine , microbiology and biotechnology , pathology , immunology , biology , isomerase , enzyme , gene
Background:Oxidative stress is a general, early feature of several neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Importantly, it has been shown that oxidative stress leads to the oxidation of specific proteins including the peptidyl-prolyl isomerase Pin1 in AD, and a-synuclein in PD. These proteins, in their oxidized form, may thus serve as new biomarkers for the early diagnosis of disease. We aim to develop sensitive assays for the quantification of oxidized Pin1 and a -synuclein in cerebrospinal fluid (CSF), and to clinically validate their use as diagnostic biomarkers for AD and PD, respectively. Methods: Sensitive sandwich ELISAs were developed for the quantification of oxidised Pin1 and a-synuclein using a combination of antibodies whereby one antibody is directed against the protein of interest and the other against oxidized groups of the protein, in the form of DNPH-derivatised carbonyl groups. Results: We successfully developed sandwich ELISAs for the specific measurement of oxidized recombinant Pin1 and oxidized recombinant asynuclein. We successfully measured oxPin1 in brain tissue extracts and we will present the results of the CSF analyses of these oxidized proteins in CSF of AD and PD patients compared to controls. Conclusions: We have developed novel ELISAs in which the oxidized from of the proteins Pin1 and a-synuclein can be measured. These ELISAs are used in clinical cohorts to evaluate the potential of these oxidized proteins in CSF as early, diagnostic biomarkers for AD and PD.