Citations 2
Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity
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Paule‐Joanne , Pierre, Bellec, Kostopoulos, Penelope, Étienne, Pierre , Tariot, Pierre N. , Orban, Pierre , Hoge, Rick, Thomas, Ronald J. , Gauthier, Serge , Craft, Suzanne , Montine, Thomas J. , Nair, Vasavan, Bohbot, Véronique D. , Venugopalan, Vinod, Ituria‐Medina, Yasser, Khachaturian, Zaven S., Teigner, Eduard, Anthal, Elena, Yu, Elsa, Ferdinand, Fabiola, Pogossova, Galina, Mayrand, Ginette, Duclair, Guerda, Gagné, Guylaine, Newbold‐Fox, Holly, Leppert, Illana, Tremblay‐Mercier, Jennifer , Frenette, Joanne, Frappier, Josée, Kat, Justin, Miron, Justin , Wan, Karen, Mahar, Laura, Carmo, Leopoldina, Théroux, Louise, Dufour, Marianne, Lafaille‐Magnan, Marie‐Élyse, Savard, Mélissa, Tuwaig, Miranda, Petkova, Mirela, Rioux, Pierre, Meyer, P.T., El‐Khoury, Rana, Gordon, Renee, Giles, Renuka, Das, Samir, Wang, Seqian, Tabrizi, Shirin , Mathotaarachchi, Sulantha , Dubuc, Sylvie, Lee, Tanya , Beaudry, Thomas, Gervais, Valérie, Pagé, Véronique, Desautels, René, Benbouhoud, Fatiha, Saint‐Fort, Eunice Farah, Verfaillie, Sander C.J. , Farzin, Sarah , Salaciak, Alyssa , Tullo, Stéphanie , Daoust, Leslie‐Ann, Köbe, Theresa , McSweeney, Melissa, Nilsson, Nathalie , Pishnamazi, Morteza, Bedetti, Christophe , Hudon, Louise, Greco, Claudia, Chapleau, Marianne , St‐Onge, Frédéric , Boutin, Sophie , Geddes, Maiya R. , Ducharme, Simon , Jean, Gabriel, Sylvain, Elisabeth, Élie, Marie‐Josee, Leblond‐Baccichet, Gloria, Soucy, Jean‐Paul , Ozlen, Hazal , Bailly, Julie, Mohammediyan, Béry, Chen, Yalin , Remz, Jordana, Rentz, Dorene M., Amariglio, Rebecca E. , Blacker, Deborah , Chhatwal, Jasmeer P. , Dickerson, Brad C., Donovan, Nancy J. , Farrell, Michelle E. , Gómez, Cristina Lois, Marshall, Gad A. , Oaoo, Kate, Price, Julie, Prokopiou, Prokopis C. , Reynolds, Gretchen , Skylar-Scott, Irina A., Vila‐Castelar, Clara , Yang, Hyun‐Sik , Trojanowki, John Q., Green, Robert C, Perrin, Richard J. , Shaw, Leslie M. , Potter, William Z. , Bernard, Marie , Jackson, Jonathan, Masliah, Eliezer , 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JAMA | June 16, 2025 | Volume: 334 | Issue: 3 | Pages: 229
Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.
Sex Differences in Longitudinal Tau-PET in Preclinical Alzheimer Disease
Coughlan, Gillian , Klinger, Hannah M , Boyle, Rory , Binette, Alexa Pichet , Christenson, Luke R., Chadwick, Trevor, Healy, Brian C. , Jonaitis, Erin M. , Jack, Clifford R. , Johnson, Keith A. , Langhough, Rebecca E., Properzi, Michael J , Seto, Mabel , Johnson, Sterling C., Shirzadi, Zahra , Yau, Wai‐Ying Wendy , Initiative, Alzheimer’s Disease Neuroimaging, Hurko, Orest, Black, Sanra E, Doody, Rachelle S., Doraiswamy, Murali, Gamst, Anthony, Scharre, Doug, Sperling, Reisa, Weiner, Michael W. , Green, Robert C, Christenson, Luke, Jack, Clifford R , Pichet Binette, Alexa , Betthauser, Tobey J. , Hansson, Oskar , Harrison, Theresa M. , Jacobs, Heidi I.L. , Hanseeuw, Bernard , Rentz, Dorene M. , Schultz, Aaron P. , Smith, Ruben , Johnson, Sterling C. , Mielke, Michelle M. , Manson, JoAnn E. , Sperling, Reisa Anne , Vemuri, Prashanthi , Buckley, Rachel F. , Initiative, Alzheimer’s Disease Neuroimaging, Black, Sanra E, Kaye, Jeffrey , Obisesan, Thomas O. , Rusinek, Henry
JAMA Neurology | March 3, 2025 | Volume: 82 | Issue: 4 | Pages: 364
Importance Alzheimer disease (AD) predominates in females at almost twice the rate relative to males. Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusive. Objective To examine whether female sex is associated with faster tau accumulation in the setting of high Aβ (as measured with positron emission tomography [PET]) and the moderating influence of sex on the association between APOE ε4 carrier status and tau accumulation. Data Sources This meta-analysis used data from 6 longitudinal aging and AD studies, including the Alzheimer’s Disease Neuroimaging Initiative, Berkeley Aging Cohort Study, BioFINDER 1, Harvard Aging Brain Study, Mayo Clinic Study of Aging, and Wisconsin Registry for Alzheimer Prevention. Longitudinal data were collected between November 2004 and May 2022. Study Selection Included studies required available longitudinal [ 18 F]flortaucipir or [ 18 F]-MK-6240 tau-PET scans, as well as baseline [ 11 C] Pittsburgh Compound B, [ 18 F]flutemetamol or [ 18 F]florbetapir Aβ-PET scans. Recruitment criteria varied across studies. Analyses began on August 7, 2023, and were completed on February 5, 2024. Data Extraction and Synthesis In each study, primary analyses extracted estimates for the sex (female or male) and the sex by baseline Aβ-PET status (high or low) association with longitudinal tau-PET using a series of mixed-effects models. Secondary mixed-effects models extracted the interaction estimate for the association of sex by APOE ε4 carrier status with longitudinal tau-PET. Study-specific estimates for each mixed-effects model were then pooled in a meta-analysis, and the global fixed effect (β) and total heterogeneity ( I 2 ) across studies were estimated. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures Seven tau-PET outcomes that showed cross-sectional sex differences were examined across temporal, parietal, and occipital lobes. Results Among 6 studies assessed, there were 1376 participants (761 [55%] female; mean [range] age at first tau scan, 71.9 [46-93] years; 401 participants [29%] with high baseline Aβ; 412 APOE ε4 carriers [30%]). Among individuals with high baseline Aβ, female sex was associated with faster tau accumulation localized to inferior temporal (β = −0.14; 95% CI, −0.22 to −0.06; P = .009) temporal fusiform (β = −0.13; 95% CI, −0.23 to −0.04; P = .02), and lateral occipital regions (β = −0.15; 95% CI, −0.24 to −0.06; P = .009) compared with male sex. Among APOE ε4 carriers, female sex was associated with faster inferior-temporal tau accumulation (β = −0.10; 95% CI, −0.16 to −0.03; P = .01). Conclusions and Relevance These findings suggest that sex differences in the pathological progression of AD call for sex-specific timing considerations when administrating anti-Aβ and anti-tau treatments.