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Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration

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Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration. / Foulds, Penny; Davidson, Yvonne; Mishra, Manjari; Hobson, David J; Humphreys, Kirsty M; Taylor, Mark; Johnson, Nancy; Weintraub, Sandra; Akiyama, Haruhiko; Arai, Tetsuaki; Hasegawa, Masato; Bigio, Eileen H; Benson, Fiona E; Allsop, David; Mann, David M A.

In: Acta Neuropathologica, Vol. 118, No. 5, 2009, p. 647-658.

Research output: Contribution to journalJournal article

Harvard

Foulds, P, Davidson, Y, Mishra, M, Hobson, DJ, Humphreys, KM, Taylor, M, Johnson, N, Weintraub, S, Akiyama, H, Arai, T, Hasegawa, M, Bigio, EH, Benson, FE, Allsop, D & Mann, DMA 2009, 'Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration', Acta Neuropathologica, vol. 118, no. 5, pp. 647-658. https://doi.org/10.1007/s00401-009-0594-0

APA

Foulds, P., Davidson, Y., Mishra, M., Hobson, D. J., Humphreys, K. M., Taylor, M., Johnson, N., Weintraub, S., Akiyama, H., Arai, T., Hasegawa, M., Bigio, E. H., Benson, F. E., Allsop, D., & Mann, D. M. A. (2009). Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration. Acta Neuropathologica, 118(5), 647-658. https://doi.org/10.1007/s00401-009-0594-0

Vancouver

Foulds P, Davidson Y, Mishra M, Hobson DJ, Humphreys KM, Taylor M et al. Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration. Acta Neuropathologica. 2009;118(5):647-658. https://doi.org/10.1007/s00401-009-0594-0

Author

Foulds, Penny ; Davidson, Yvonne ; Mishra, Manjari ; Hobson, David J ; Humphreys, Kirsty M ; Taylor, Mark ; Johnson, Nancy ; Weintraub, Sandra ; Akiyama, Haruhiko ; Arai, Tetsuaki ; Hasegawa, Masato ; Bigio, Eileen H ; Benson, Fiona E ; Allsop, David ; Mann, David M A. / Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration. In: Acta Neuropathologica. 2009 ; Vol. 118, No. 5. pp. 647-658.

Bibtex

@article{530f890e7cb1484db64ff24f4a9d3107,
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.",
keywords = "Adult, Aged, Aged, 80 and over, Brain, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Female, Frontotemporal Lobar Degeneration, Humans, Male, Middle Aged, Phosphorylation, Statistics as Topic, tau Proteins",
author = "Penny Foulds and Yvonne Davidson and Manjari Mishra and Hobson, {David J} and Humphreys, {Kirsty M} and Mark Taylor and Nancy Johnson and Sandra Weintraub and Haruhiko Akiyama and Tetsuaki Arai and Masato Hasegawa and Bigio, {Eileen H} and Benson, {Fiona E} and David Allsop and Mann, {David M A}",
year = "2009",
doi = "10.1007/s00401-009-0594-0",
language = "English",
volume = "118",
pages = "647--658",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "5",

}

RIS

TY - JOUR

T1 - Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration

AU - Foulds, Penny

AU - Davidson, Yvonne

AU - Mishra, Manjari

AU - Hobson, David J

AU - Humphreys, Kirsty M

AU - Taylor, Mark

AU - Johnson, Nancy

AU - Weintraub, Sandra

AU - Akiyama, Haruhiko

AU - Arai, Tetsuaki

AU - Hasegawa, Masato

AU - Bigio, Eileen H

AU - Benson, Fiona E

AU - Allsop, David

AU - Mann, David M A

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Brain

KW - DNA-Binding Proteins

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Frontotemporal Lobar Degeneration

KW - Humans

KW - Male

KW - Middle Aged

KW - Phosphorylation

KW - Statistics as Topic

KW - tau Proteins

U2 - 10.1007/s00401-009-0594-0

DO - 10.1007/s00401-009-0594-0

M3 - Journal article

C2 - 19823856

VL - 118

SP - 647

EP - 658

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 5

ER -