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TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration

Foulds, Penelope and McAuley, Erica and Gibbons, Linda and Davidson, Yvonne and Pickering-Brown, Stuart M and Neary, David and Snowden, Julie S and Allsop, David and Mann, David M A (2008) TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration. Acta Neuropathologica, 116 (2). pp. 141-146. ISSN 0001-6322

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Abstract

Autopsy studies have shown that about 55% of patients with frontotemporal lobar degeneration (FTLD) and 25% of patients with Alzheimer's disease (AD) harbour TDP-43 immunoreactive pathological changes in their brains. Using ELISA, we investigated whether we could detect the presence, or increased amounts, of TDP-43 in plasma of patients with FTLD and AD compared to normal control subjects. We detected elevated levels of TDP-43 protein in plasma of 46% patients with FTLD with clinical frontotemporal dementia (FTD) and 22% patients with AD, compared to 8% of control subjects. The proportions of patients with FTD and AD showing raised plasma TDP-43 levels correspond closely to those proportions known from autopsy studies to contain TDP-43 pathological changes in their brains. Raised TDP-43 plasma levels may thereby index TDP-43 pathology within the brain. Plasma TDP-43 levels may be a biomarker that can provide a laboratory test capable of identifying the presence of TDP-43 brain pathology in neurodegenerative disease during life. It may help to distinguish those cases of FTLD with ubiquitin/TDP-43 pathology in their brains from those with tauopathy. As a predictive test, plasma TDP-43 level may have great practical value in directing therapeutic strategies aimed at preventing or removing tau or TDP-43 pathological changes from the brain in FTLD and AD.

Item Type: Article
Journal or Publication Title: Acta Neuropathologica
Uncontrolled Keywords: Adult ; Aged ; Alzheimer Disease ; Biological Markers ; Brain ; DNA-Binding Proteins ; Dementia ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoprecipitation ; Male ; Middle Aged
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 53095
Deposited By: ep_importer_pure
Deposited On: 09 Mar 2012 02:50
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 19:43
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/53095

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