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Tau levels in platelets isolated from Huntington's disease patients serve as a biomarker of disease severity.

Published version
Peer-reviewed

Repository DOI


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Abstract

Tau is a microtubule protein that is known to be hyperphosphorylated and to aggregate in several chronic neurodegenerative disorders. In many cases, in particular in Alzheimer's disease, the degree of tau pathology has been demonstrated to correlate with cognitive deficits and/or decline. In Huntington's disease (HD), a dominantly inherited neurodegenerative disorder, both cognitive impairments and abnormal tau expression have been reported to occur, along with the accumulation of the mutant huntingtin protein. In this respect, tau has been shown to be present in the cerebrospinal fluid of individuals with HD and to increase with disease progression. However, how this relates to changes in tau found in the periphery is largely unknown. In this study, we collected blood samples from patients with HD and isolated multiple blood components including plasma, platelets, and peripheral blood mononuclear cells to measure their tau levels and subsequently correlate these to cognitive impairments and disease stage. Our results suggest that the amount of tau, particularly N-terminal tau (NTA-tau) and total tau (t-tau), is elevated in all assayed blood components and that the quantity of tau within platelets, specifically, is strongly correlated with disease severity.

Description

Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024


Funder: Huntington's Disease Society of America; doi: http://dx.doi.org/10.13039/100000887


Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100010269


Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265


Funder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956

Journal Title

J Neurol

Conference Name

Journal ISSN

0340-5354
1432-1459

Volume Title

272

Publisher

Springer Science and Business Media LLC

Rights and licensing

Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Sponsorship
Vetenskapsrådet (2017-00915, 2022-00732, ALFGBG-715986, ALFGBG-965240, 2023-00356, 2022-01018, 2019-02397, ALFGBG-71320)
Alzheimerfonden (AF-930351, AF-939721, AF-968270)
Hjärnfonden (FO2017-0243, ALZ2022-0006, FO2022-0270)
EU Joint Programme – Neurodegenerative Disease Research (JPND2019-466-236, JPND2021-00694)
Alzheimer's Association (ZEN-21-848495, SG-23-1038904 QC, ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C, ADSF-24-1284328-C)
European Union’s Horizon Europe research and innovation programme (101053962)
Alzheimer's Drug Discovery Foundation (201809-2016862)
European Partnership on Metrology (#22HLT07)
HORIZON EUROPE Marie Sklodowska-Curie Actions (860197)
UK Dementia Research Institute (UKDRI-1003)