Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease

Horie, Kanta ; Salvadó, Gemma LU ; Barthélemy, Nicolas R. ; Janelidze, Shorena LU ; Li, Yan ; He, Yingxin ; Saef, Benjamin ; Chen, Charles D. ; Jiang, Hong and Strandberg, Olof LU , et al. (2023) In Nature Medicine 29(8). p.1954-1963
Abstract

Aggregated insoluble tau is one of two defining features of Alzheimer’s disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight... (More)

Aggregated insoluble tau is one of two defining features of Alzheimer’s disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219). MTBR-tau243 was most strongly associated with tau-positron emission tomography (PET) and cognition, whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 ≤ R 2 ≤ 0.75) and the performance in predicting cognitive measures (0.34 ≤ R 2 ≤ 0.48) approached that of tau-PET (0.44 ≤ R 2 ≤ 0.52). MTBR-tau243 levels longitudinally increased with insoluble tau aggregates, unlike CSF p-tau species. CSF MTBR-tau243 is a specific biomarker of tau aggregate pathology, which may be utilized in interventional trials and in the diagnosis of patients. Based on these findings, we propose to revise the A/T/(N) criteria to include MTBR-tau243 as representing insoluble tau aggregates (‘T’).

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
29
issue
8
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:37443334
  • scopus:85164793186
ISSN
1078-8956
DOI
10.1038/s41591-023-02443-z
language
English
LU publication?
yes
id
0a34be14-1b80-4749-bad1-46e1a01f9d01
date added to LUP
2023-09-25 15:17:47
date last changed
2024-04-19 02:41:41
@article{0a34be14-1b80-4749-bad1-46e1a01f9d01,
  abstract     = {{<p>Aggregated insoluble tau is one of two defining features of Alzheimer’s disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219). MTBR-tau243 was most strongly associated with tau-positron emission tomography (PET) and cognition, whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 ≤ R <sup>2</sup> ≤ 0.75) and the performance in predicting cognitive measures (0.34 ≤ R <sup>2</sup> ≤ 0.48) approached that of tau-PET (0.44 ≤ R <sup>2</sup> ≤ 0.52). MTBR-tau243 levels longitudinally increased with insoluble tau aggregates, unlike CSF p-tau species. CSF MTBR-tau243 is a specific biomarker of tau aggregate pathology, which may be utilized in interventional trials and in the diagnosis of patients. Based on these findings, we propose to revise the A/T/(N) criteria to include MTBR-tau243 as representing insoluble tau aggregates (‘T’).</p>}},
  author       = {{Horie, Kanta and Salvadó, Gemma and Barthélemy, Nicolas R. and Janelidze, Shorena and Li, Yan and He, Yingxin and Saef, Benjamin and Chen, Charles D. and Jiang, Hong and Strandberg, Olof and Pichet Binette, Alexa and Palmqvist, Sebastian and Sato, Chihiro and Sachdev, Pallavi and Koyama, Akihiko and Gordon, Brian A. and Benzinger, Tammie L.S. and Holtzman, David M. and Morris, John C. and Mattsson-Carlgren, Niklas and Stomrud, Erik and Ossenkoppele, Rik and Schindler, Suzanne E. and Hansson, Oskar and Bateman, Randall J.}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1954--1963}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41591-023-02443-z}},
  doi          = {{10.1038/s41591-023-02443-z}},
  volume       = {{29}},
  year         = {{2023}},
}