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O1‐12‐06: MHPG as an additional marker for the differentiation of dementia with Lewy bodies from Alzheimer's disease, vascular dementia and frontotemporal dementia
Author(s) -
Herbert Megan,
Aerts Marjolein,
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.2012.05.2131
Subject(s) - frontotemporal dementia , dementia , dementia with lewy bodies , vascular dementia , psychology , frontotemporal lobar degeneration , lewy body , medicine , tau protein , biomarker , alzheimer's disease , cerebrospinal fluid , neuroscience , pathology , disease , chemistry , biochemistry
neous disease, characterized by atrophy of the frontal and temporal lobes. It is the second most common form of dementia after Alzheimer’s disease (AD), and clinically characterized by behavioural and/or language dysfunction. At the pathological level, most cases are either characterized by the presence of tau inclusions (FTLD-tau), or the presence of TDP-43 inclusions (FTLD-TDP). Although neuropathology seems to be linked to the clinical picture, there are no CSF biomarkers available to diagnose these FTLD subtypes. We aim to quantify both tau and TDP-43 proteins in the cerebrospinal fluid (CSF) and to analyse if a combination of these can function as biomarker to improve discrimination of FTLD subtypes. Methods:We optimized our previously developed TDP-43 ELISA (1) for quantification in CSF. We used post-mortem obtained, pathology-confirmed ventricular CSF to quantify TDP-43, and total and phosphorylated tau (t-tau, p-tau) levels by ELISA. Statistical analyses were performed to determine the optimal combination of markers for discriminating FTLDtau and FTLD-TDP cases. Results: Our analysis showed that from the tested markers, quantification of a combination of TDP-43 and t-tau in ventricular CSF results in the most optimal differentiation of FTLD-tau and FTLD-TDP cases. These combined markers could significantly differentiate the subtypes with a sensitivity of 64% and specificity of 93%. Conclusions: This is the first study to combine the quantification of CSF tau and TDP-43 levels of FTLD cases. Although either biomarker alone did not discriminate FTLD subtypes, combined analysis of TDP-43 and t-tau significantly improved this differentiation. It remains to be shown if TDP-43 in its pathological, phosphorylated form may even further improve this differentiation. We conclude that ante-mortem CSF analysis based on t-tau and TDP-43 levels might aid in the diagnosis of FTLD subtypes, and possibly, the differentiation from AD.