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@ARTICLE{McDade:281435,
author = {McDade, Eric M and Barthélemy, Nicolas R and Wang, Guoqiao
and Li, Yan and Cao, Yuchen and Gordon, Brian and Benzinger,
Tammie L S and Clifford, David and Goate, Alison M and
Renton, Alan E and Hassenstab, Jason and Llibre-Guerra,
Jorge J and Perrin, Richard J and Xiong, Chengjie and
Cruchaga, Carlos and Mummery, Catherine J and Berman, Sarah
B and Lah, James and Roberson, Erik D and Van Dyck,
Christopher and Gauthier, Serge and Masters, Colin L and
Masellis, Mario and Bittner, Tobias and Yaari, Roy and
Chhatwal, Jasmeer and Chrem, Patricio and Brooks, William
and Suzuki, Kazushi and Levin, Johannes J and Jucker,
Mathias and Ringman, John and Wallon, David and Ikeuchi,
Takeshi and Lee, Jae-Hong and Roh, Jee Hoon and Schofield,
Peter and Fox, Nick C and Ryan, Natalie S and Vöglein,
Jonathan and Karch, Celeste and Ibáñez, Laura and Day,
Gregory S and Sánchez-Valle, Raquel and Daniels, Alisha and
Morris, John C and Supnet-Bell, Charlene and Levey, Allan I
and Bateman, Randall J and Team, DIAN-TU Study},
collaboration = {Team, DIAN Obs},
title = {{T}he relationship of soluble tau species with
{A}lzheimer's disease amyloid plaque removal and tau
pathology.},
journal = {Alzheimer's and dementia},
volume = {21},
number = {9},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DZNE-2025-01120},
pages = {e70689},
year = {2025},
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.},
keywords = {Humans / tau Proteins: cerebrospinal fluid / Alzheimer
Disease: cerebrospinal fluid / Alzheimer Disease: pathology
/ Alzheimer Disease: drug therapy / Plaque, Amyloid:
pathology / Plaque, Amyloid: drug therapy / Plaque, Amyloid:
cerebrospinal fluid / Male / Antibodies, Monoclonal,
Humanized: therapeutic use / Female / Biomarkers:
cerebrospinal fluid / Amyloid beta-Peptides /
Phosphorylation / Middle Aged / Aged / amyloid beta plaque
reduction (Other) / dominantly inherited Alzheimer's disease
(Other) / microtubule‐binding region (Other) /
phosphorylated tau (Other) / tau Proteins (NLM Chemicals) /
Antibodies, Monoclonal, Humanized (NLM Chemicals) /
Biomarkers (NLM Chemicals) / Amyloid beta-Peptides (NLM
Chemicals) / gantenerumab (NLM Chemicals) / solanezumab (NLM
Chemicals)},
cin = {Clinical Research (Munich) / AG Levin / AG Jucker},
ddc = {610},
cid = {I:(DE-2719)1111015 / I:(DE-2719)1111016 /
I:(DE-2719)1210001},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40985290},
doi = {10.1002/alz.70689},
url = {https://pub.dzne.de/record/281435},
}