Journal Article

DZNE-2025-01120

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.

McDade, E. M. ; Barthélemy, N. R. ; Wang, G. ; Li, Y. ; Cao, Y. ; Gordon, B. ; Benzinger, T. L. S. ; Clifford, D. ; Goate, A. M. ; Renton, A. E. ; Hassenstab, J. ; Llibre-Guerra, J. J. ; Perrin, R. J. ; Xiong, C. ; Cruchaga, C. ; Mummery, C. J. ; Berman, S. B. ; Lah, J. ; Roberson, E. D. ; Van Dyck, C. ; Gauthier, S. ; Masters, C. L. ; Masellis, M. ; Bittner, T. ; Yaari, R. ; Chhatwal, J. ; Chrem, P. ; Brooks, W. ; Suzuki, K. ; Levin, J. J.DZNE* ; Jucker, M.DZNE* ; Ringman, J. ; Wallon, D. ; Ikeuchi, T. ; Lee, J.-H. ; Roh, J. H. ; Schofield, P. ; Fox, N. C. ; Ryan, N. S. ; Vöglein, J.DZNE* ; Karch, C. ; Ibáñez, L. ; Day, G. S. ; Sánchez-Valle, R. ; Daniels, A. ; Morris, J. C. ; Supnet-Bell, C. ; Levey, A. I. ; Bateman, R. J. ; Team, D. S. ; Team, D. O. (Collaboration Author)

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.70689

Abstract: Tau-derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid-beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long-term anti-Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them.A post-hoc analysis of the DIAN-TU-001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab (n = 50), gantenerumab (n = 52), or placebo (n = 40). High-resolution mass spectrometry quantified CSF tau species over four years.Phosphorylated tau (p-tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab-mediated Aβ plaque reduction. Nearly a decade later, MTBR-tau243 and p-tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression.Initially changing soluble p-tau species track Aβ plaque reduction, while ptau205 and MTBR-243 reflect tau tangle pathology, informing different pathways of therapeutic strategies.p-tau217 and p-tau231 correlate with Aβ-PET and respond to Aβ-plaque lowering therapies. Aβ immunotherapy trials support a direct link between p-tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT-related biomarkers. Blood-based p-tau217 assays may provide a non-invasive tool to monitor Aβ therapies. MTBR-tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT-targeting therapies.

Keyword(s): Humans (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: drug therapy (MeSH) ; Plaque, Amyloid: pathology (MeSH) ; Plaque, Amyloid: drug therapy (MeSH) ; Plaque, Amyloid: cerebrospinal fluid (MeSH) ; Male (MeSH) ; Antibodies, Monoclonal, Humanized: therapeutic use (MeSH) ; Female (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides (MeSH) ; Phosphorylation (MeSH) ; Middle Aged (MeSH) ; Aged (MeSH) ; amyloid beta plaque reduction ; dominantly inherited Alzheimer's disease ; microtubule‐binding region ; phosphorylated tau ; tau Proteins ; Antibodies, Monoclonal, Humanized ; Biomarkers ; Amyloid beta-Peptides ; gantenerumab ; solanezumab

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Clinical Neurodegeneration (AG Levin)
3. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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