title: Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration.
abstract: In the present study, we have correlated plasma TDP-43 levels, as measured by ELISA, with the presence of TDP-43 pathological changes in the brains of 28 patients with frontotemporal lobar degeneration (FTLD) (14 with FTLD-TDP and 14 with FTLD-tau) and 24 patients with pathologically confirmed AD (8 with, and 16 without, TDP-43 pathological changes). Western blotting revealed full-length TDP-43, including a phosphorylated form, and a phosphorylated C-terminal fragment, in all samples examined. Both ELISA and immunohistochemistry were performed using phospho-dependent and phospho-independent TDP-43 antibodies for detection of phosphorylated and total TDP-43, respectively. Over all 52 cases, plasma levels of TDP-43, and scores of brain TDP-43 pathology, determined using TDP-43 phospho-dependent antibody correlated with the equivalent measure determined using the TDP phospho-independent antibody. In FTLD, but not AD, TDP-43 plasma levels correlated significantly with the pathology score when using the TDP-43 phospho-dependent antibody, but a similar correlation was not seen in either FTLD or AD using the TDP-43 phospho-independent antibody. With the TDP-43 phospho-independent antibody, there were no significant differences in median plasma TDP-43 levels between FTLD, or AD, patients with or without TDP-43 pathology. Using TDP-43 phospho-dependent antibody, median plasma TDP-43 levels were greater in patients with, than in those without, TDP-43 pathology for FTLD patients, though not significantly so, but not for AD patients. Present assays for TDP-43 do not differentiate between FTLD, or AD, patients with or without TDP-43 pathological changes in their brains. However, the levels of phosphorylated TDP-43 in plasma do correlate with the extent of TDP-43 brain pathology in FTLD, and therefore might be a useful surrogate marker for tracking changes in TDP-43 brain pathology during the course of this disease.
authors.affiliation: Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Penelope G
authors.initials: PG
authors.lastname: Foulds
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Davidson
authors.forename: Manjari
authors.initials: M
authors.lastname: Mishra
authors.forename: David J
authors.initials: DJ
authors.lastname: Hobson
authors.forename: Kirsty M
authors.initials: KM
authors.lastname: Humphreys
authors.forename: Mark
authors.initials: M
authors.lastname: Taylor
authors.forename: Nancy
authors.initials: N
authors.lastname: Johnson
authors.forename: Sandra
authors.initials: S
authors.lastname: Weintraub
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Benson
authors.forename: David
authors.initials: D
authors.lastname: Allsop
authors.forename: David M A
authors.initials: DM
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000097:blood* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D013223:Statistics as Topic; D016875:tau Proteins / Q000097:blood
chemical_list: D004268:DNA-Binding Proteins; D016875:tau Proteins