Citations 3
The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology
McDade, Eric , Barthélemy, Nicolas R. , Wang, Guoqiao , Li, Yan , Cao, Yuchen , Clifford, David B., Goate, Alison , Renton, Alan E., Hassenstab, Jason , Perrin, Richard J. , Xiong, Chengjie , Mummery, Catherine J. , Berman, Sarah , Roberson, Erik D. , Dyck, Christopher van , Gauthier, Serge , Masters, Colin L. , Bittner, Tobias , Yaari, R. , Chhatwal, Jasmeer P. , Chrem, Patricio, Xiong, Chengjie , Ringman, John M. , Ryan, Natalie S. , Day, Gregory S. , Daniels, Alisha , Morris, John C., Supnet, Charlene , Team, The DIAN‐TU Study Team and DIAN Obs, McDade, Eric M , Bateman, Randall J , Roberson, Erik , Day, Gregory S , Masters, Colin L , Xiong, Chengjie , Hassenstab, Jason , Goate, Alison M , Supnet-Bell, Charlene , Berman, Sarah , Gordon, Brian A. , Benzinger, Tammie L.S. , Renton, Alan , Llibre‐Guerra, Jorge J. , Xiong, Chengjie , Cruchaga, Carlos , Lah, James J. , Masellis, Mario , Brooks, William S. , Suzuki, Kazushi , Jucker, Mathias , Wallon, David , Ikeuchi, Takeshi , Lee, Jae‐Hong , Roh, Jee Hoon , Schofield, Peter R. , Fox, Nick C. , Vöglein, Jonathan , Karch, Celeste M. , Ibanez, Laura , Sánchez‐Valle, Raquel , Morris, John C. , Levey, Allan I. , Bateman, Randall J. , Team, The DIAN‐TU Study Team and DIAN Obs
Alzheimer's & Dementia | September 23, 2025 | Volume: 21 | Issue: 9 | Pages: No page available
Abstract BACKGROUND 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. METHODS 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. RESULTS 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. DISCUSSION 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. Highlights 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.
The CentiMarker project: Standardizing quantitative Alzheimer's disease fluid biomarkers for biologic interpretation
Wang, Guoqiao , Li, Yan, Xiong, Chengjie , Cao, Yuchen , Blennow, Kaj, Dage, Jeffrey L. , Jack, Clifford R. , Shaw, Leslie M. , Initiative, the Alzheimer's Disease Neuroimaging, Bateman, Randall J., Wang, Guoqiao , Jack, Clifford R , Dage, Jeffrey L , Li, Yan , Xiong, Chengjie , Cao, Yuchen, Schindler, Suzanne E. , McDade, Eric , Blennow, Kaj , Hansson, Oskar , Teunissen, Charlotte E. , Zetterberg, Henrik , Ibanez, Laura , Timsina, Jigyasha , Cruchaga, Carlos , Initiative, the Alzheimer's Disease Neuroimaging, Bateman, Randall J.
Alzheimer's & Dementia | April 16, 2025 | Volume: 21 | Issue: 4 | Pages: No page available
Abstract INTRODUCTION Biomarkers play a crucial role in understanding Alzheimer's disease (AD) pathogenesis and treatment effects. However, comparing biomarker measures without standardization and appreciating their magnitude relative to the disease can be challenging. METHODS To address this issue, we propose the CentiMarker approach, similar to Centiloid, which provides a standardized scale between normal (0) and nearly maximum abnormal AD (100) ranges. We applied this scale to cerebrospinal fluid (CSF) biomarkers in dominantly inherited AD and sporadic AD cohorts. RESULTS CentiMarkers facilitated the interpretation of disease abnormality, demonstrating comparable changes and distributions of AD biomarkers across disease stages. CentiMarkers make the treatment effect more comparable than their original scales across various biomarkers. DISCUSSION The versatility of CentiMarkers makes it a valuable tool for standardized biomarker comparison in AD research, enabling informed cross‐study comparisons and contributing to accelerated therapeutic development. Adoption of the CentiMarker scale could enhance biomarker reporting and advance our understanding of AD. Highlights Comparing fluid biomarkers without appreciating their magnitude relative to the disease can be challenging. We propose a CentiMarker metric to standardize biomarker measures from normal (0) and nearly maximum abnormal AD (100) ranges. CentiMarkers make the treatment effect more comparable across various biomarkers than when using the original scales.
The landscape of autosomal-dominant Alzheimer’s disease: global distribution and age of onset
Liu, Haiyan , Marsh, Thomas W. , Shi, Xinyu , Bowling, Kevin M. , Ziegemeier, Ellen , Wang, Guoqiao , Cao, Yuchen , Aristel, Alisha, Li, Jessie, Dickson, Alexa , Perrin, Richard J. , Goate, Alison , Fernández, María Victoria , Day, Gregory S. , Doering, Michelle , Daniels, Alisha , Hassenstab, Jason , Supnet, Charlene , Xiong, Chengjie , Berman, Sarah , Ryan, Natalie S. , Huey, Edward D. , Noble, James M. , Roh, Jee Hoon , Laske, Christoph , Sánchez‐Valle, Raquel , Méndez, Patricio Chrem, Chhatwal, Jasmeer P. , Farlow, Martin R. , Xiong, Chengjie , Gordon, Brian A , Ibanez, Laura , Vöglein, Jonathan , Roh, Jee Hoon , Ikeuchi, T , Sánchez-Valle, Raquel , Chhatwal, Jasmeer , Xiong, Chengjie , Rosa-Neto, Pedro , Schofield, Peter R , Bateman, Randall J , Cruchaga, Carlos , Day, Gregory S , Hassenstab, Jason , Fernandez, Maria , Goate, Alison M , Supnet-Bell, Charlene , Berman, Sarah , Noble, James M , Renton, Alan , Gordon, Brian A. , Benzinger, Tammie L.S. , Allegri, Ricardo , Fox, Nick C. , Vöglein, Jonathan , Jucker, Mathias , Ikeuchi, Takeshi , Schofield, Peter R. , Lee, Jae‐Hong , Levey, Allan I. , Lopera, Francisco Javier , Martins, Ralph N. , Niimi, Yoshiki , Bateman, Randall J. , Karch, Celeste M. , McDade, Eric , Llibre‐Guerra, Jorge J.
Brain | February 4, 2025 | Volume: 148 | Issue: 7 | Pages: 2429-2440
Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.