TY  - JOUR
AU  - McDade, Eric M
AU  - Barthélemy, Nicolas R
AU  - Wang, Guoqiao
AU  - Li, Yan
AU  - Cao, Yuchen
AU  - Gordon, Brian
AU  - Benzinger, Tammie L S
AU  - Clifford, David
AU  - Goate, Alison M
AU  - Renton, Alan E
AU  - Hassenstab, Jason
AU  - Llibre-Guerra, Jorge J
AU  - Perrin, Richard J
AU  - Xiong, Chengjie
AU  - Cruchaga, Carlos
AU  - Mummery, Catherine J
AU  - Berman, Sarah B
AU  - Lah, James
AU  - Roberson, Erik D
AU  - Van Dyck, Christopher
AU  - Gauthier, Serge
AU  - Masters, Colin L
AU  - Masellis, Mario
AU  - Bittner, Tobias
AU  - Yaari, Roy
AU  - Chhatwal, Jasmeer
AU  - Chrem, Patricio
AU  - Brooks, William
AU  - Suzuki, Kazushi
AU  - Levin, Johannes J
AU  - Jucker, Mathias
AU  - Ringman, John
AU  - Wallon, David
AU  - Ikeuchi, Takeshi
AU  - Lee, Jae-Hong
AU  - Roh, Jee Hoon
AU  - Schofield, Peter
AU  - Fox, Nick C
AU  - Ryan, Natalie S
AU  - Vöglein, Jonathan
AU  - Karch, Celeste
AU  - Ibáñez, Laura
AU  - Day, Gregory S
AU  - Sánchez-Valle, Raquel
AU  - Daniels, Alisha
AU  - Morris, John C
AU  - Supnet-Bell, Charlene
AU  - Levey, Allan I
AU  - Bateman, Randall J
AU  - Team, DIAN-TU Study
TI  - The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.
JO  - Alzheimer's and dementia
VL  - 21
IS  - 9
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-01120
SP  - e70689
PY  - 2025
AB  - 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.
KW  - Humans
KW  - tau Proteins: cerebrospinal fluid
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: drug therapy
KW  - Plaque, Amyloid: pathology
KW  - Plaque, Amyloid: drug therapy
KW  - Plaque, Amyloid: cerebrospinal fluid
KW  - Male
KW  - Antibodies, Monoclonal, Humanized: therapeutic use
KW  - Female
KW  - Biomarkers: cerebrospinal fluid
KW  - Amyloid beta-Peptides
KW  - Phosphorylation
KW  - Middle Aged
KW  - Aged
KW  - amyloid beta plaque reduction (Other)
KW  - dominantly inherited Alzheimer's disease (Other)
KW  - microtubule‐binding region (Other)
KW  - phosphorylated tau (Other)
KW  - tau Proteins (NLM Chemicals)
KW  - Antibodies, Monoclonal, Humanized (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - gantenerumab (NLM Chemicals)
KW  - solanezumab (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40985290
DO  - DOI:10.1002/alz.70689
UR  - https://pub.dzne.de/record/281435
ER  -