TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration.
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.
Foulds
Penelope
P
Division of Biomedical and Life Sciences, School of Health and Medicine, University of Lancaster, Lancaster, UK.
McAuley
Erica
E
Gibbons
Linda
L
Davidson
Yvonne
Y
Pickering-Brown
Stuart M
SM
Neary
David
D
Snowden
Julie S
JS
Allsop
David
D
Mann
David M A
DM
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000097:blood*; D003704:Dementia / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D004268:DNA-Binding Proteins