%0 Journal Article
%A McDade, Eric M
%A Barthélemy, Nicolas R
%A Wang, Guoqiao
%A Li, Yan
%A Cao, Yuchen
%A Gordon, Brian
%A Benzinger, Tammie L S
%A Clifford, David
%A Goate, Alison M
%A Renton, Alan E
%A Hassenstab, Jason
%A Llibre-Guerra, Jorge J
%A Perrin, Richard J
%A Xiong, Chengjie
%A Cruchaga, Carlos
%A Mummery, Catherine J
%A Berman, Sarah B
%A Lah, James
%A Roberson, Erik D
%A Van Dyck, Christopher
%A Gauthier, Serge
%A Masters, Colin L
%A Masellis, Mario
%A Bittner, Tobias
%A Yaari, Roy
%A Chhatwal, Jasmeer
%A Chrem, Patricio
%A Brooks, William
%A Suzuki, Kazushi
%A Levin, Johannes J
%A Jucker, Mathias
%A Ringman, John
%A Wallon, David
%A Ikeuchi, Takeshi
%A Lee, Jae-Hong
%A Roh, Jee Hoon
%A Schofield, Peter
%A Fox, Nick C
%A Ryan, Natalie S
%A Vöglein, Jonathan
%A Karch, Celeste
%A Ibáñez, Laura
%A Day, Gregory S
%A Sánchez-Valle, Raquel
%A Daniels, Alisha
%A Morris, John C
%A Supnet-Bell, Charlene
%A Levey, Allan I
%A Bateman, Randall J
%A Team, DIAN-TU Study
%T The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.
%J Alzheimer's and dementia
%V 21
%N 9
%@ 1552-5260
%C Hoboken, NJ
%I Wiley
%M DZNE-2025-01120
%P e70689
%D 2025
%X 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.
%K Humans
%K tau Proteins: cerebrospinal fluid
%K Alzheimer Disease: cerebrospinal fluid
%K Alzheimer Disease: pathology
%K Alzheimer Disease: drug therapy
%K Plaque, Amyloid: pathology
%K Plaque, Amyloid: drug therapy
%K Plaque, Amyloid: cerebrospinal fluid
%K Male
%K Antibodies, Monoclonal, Humanized: therapeutic use
%K Female
%K Biomarkers: cerebrospinal fluid
%K Amyloid beta-Peptides
%K Phosphorylation
%K Middle Aged
%K Aged
%K amyloid beta plaque reduction (Other)
%K dominantly inherited Alzheimer's disease (Other)
%K microtubule‐binding region (Other)
%K phosphorylated tau (Other)
%K tau Proteins (NLM Chemicals)
%K Antibodies, Monoclonal, Humanized (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K gantenerumab (NLM Chemicals)
%K solanezumab (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40985290
%R 10.1002/alz.70689
%U https://pub.dzne.de/record/281435