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

• Published in: Acta neuropathologica Vol. 116; no. 2; pp. 141 - 146
• Main Authors: Foulds, Penelope, McAuley, Erica, Gibbons, Linda, Davidson, Yvonne, Pickering-Brown, Stuart M., Neary, David, Snowden, Julie S., Allsop, David, Mann, David M. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2008; Springer Nature B.V
• Subjects: Adult; Aged; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Autopsies; Biomarkers; Biomarkers - blood; Brain - metabolism; Brain - pathology; Brain research; Dementia; Dementia - blood; Dementia - metabolism; Dementia - pathology; Disease; DNA-Binding Proteins - blood; Enzyme-Linked Immunosorbent Assay; Female; Histology; Humans; Immunoprecipitation; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neurosciences; Original Paper; Pathology; Plasma; Proteins; United Kingdom > UK; Plasma; Frontotemporal lobar degeneration; Biomarker; Alzheimer’s disease; TDP-43
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-008-0389-8

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.