Towards a TDP-43-Based Biomarker for ALS and FTLD.

Abstract:

:TDP-43 accumulates in nerve cells of nearly all cases of amyotrophic lateral sclerosis (ALS; the commonest form of motor neuron disease) and in the majority of Tau-negative frontotemporal lobar degeneration (FTLD). There is currently no biochemical test or marker of disease activity for ALS or FTLD, and the clinical diagnosis depends on the opinion of an experienced neurologist. TDP-43 has a key role in the pathogenesis of ALS/FTLD. Measuring TDP-43 in easily accessible biofluids, such as blood or cerebrospinal fluid, might reduce diagnostic delay and offer a readout for use in future drug trials. However, attempts at measuring disease-specific forms of TDP-43 in peripheral biofluids of ALS and FTLD patients have not yielded consistent results, and only some of the pathological biochemical features of TDP-43 found in human brain tissue have been detected in clinical biofluids to date. Reflecting on the molecular pathology of TDP-43, this review provides a critical overview on biofluid studies and future directions to develop a TDP-43-based clinical biomarker for ALS and FTLD.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Feneberg E,Gray E,Ansorge O,Talbot K,Turner MR

doi

10.1007/s12035-018-0947-6

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

7789-7801

issue

10

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-0947-6

journal_volume

55

pub_type

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