Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex
Ossenkoppele R, Coomans EM, Apostolova LG, Baker SL, Barthel H, Beach TG, Benzinger TLS, Betthauser T, Bischof GN, Bottlaender M, Bourgeat P, den Braber A, Brendel M, Brickman AM, Cash DM, Carrillo MC, Coath W, Christian BT, Dickerson BC, Dore V, Drzezga A, Feizpour A, van der Flier WM, Franzmeier N, Frisoni GB, Garibotto V, van de Giessen E, Domingo-Gispert J, Gnoerich J, Gu Y, Guan Y, Hanseeuw BJ, Harrison TM, Jack CR, Jaeger E, Jagust WJ, Jansen WJ, La Joie R, Johnson KA, Johnson SC, Kennedy IA, Kim JP, van Laere K, Lagarde J, Lao P, Luchsinger JA, Kern S, Kreisl WC, Malotaux V, Malpetti M, Manly JJ, Mao X, Mattsson-Carlgren N; Mayo Clinic Study on Aging; Messerschmidt K, Minguillon C, Mormino EM, O'Brien JT, Palmqvist S, Peretti DE, Petersen RC, Pijnenburg YAL, Pontecorvo MJ, Poirier J; PREVENT-AD Research Group; Rabinovici GD, Rahmouni N, Risacher SL, Rosa-Neto P, Rosen H, Rowe CC, Rowe JB, Rullmann M, Salman Y, Sarazin M, Saykin AJ, Schneider JA, Schöll M, Schott JM, Seo SW, Serrano GE, Shcherbinin S, Shekari M, Skoog I, Smith R, Sperling RA, Spruyt L, Stomrud E, Strandberg O, Therriault J, Xie F, Vandenberghe R, Villemagne VL, Villeneuve S, Visser PJ, Vossler H, Young CB, Groot C, Hansson O
Resumen
Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. APOE ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (N = 5,072 from 3 cohorts).
Referencia
Ossenkoppele R, Coomans EM, Apostolova LG, Baker SL, Barthel H, Beach TG, Benzinger TLS, Betthauser T, Bischof GN, Bottlaender M, Bourgeat P, den Braber A, Brendel M, Brickman AM, Cash DM, Carrillo MC, Coath W, Christian BT, Dickerson BC, Dore V, Drzezga A, Feizpour A, van der Flier WM, Franzmeier N, Frisoni GB, Garibotto V, van de Giessen E, Domingo-Gispert J, Gnoerich J, Gu Y, Guan Y, Hanseeuw BJ, Harrison TM, Jack CR, Jaeger E, Jagust WJ, Jansen WJ, La Joie R, Johnson KA, Johnson SC, Kennedy IA, Kim JP, van Laere K, Lagarde J, Lao P, Luchsinger JA, Kern S, Kreisl WC, Malotaux V, Malpetti M, Manly JJ, Mao X, Mattsson-Carlgren N; Mayo Clinic Study on Aging; Messerschmidt K, Minguillon C, Mormino EM, O'Brien JT, Palmqvist S, Peretti DE, Petersen RC, Pijnenburg YAL, Pontecorvo MJ, Poirier J; PREVENT-AD Research Group; Rabinovici GD, Rahmouni N, Risacher SL, Rosa-Neto P, Rosen H, Rowe CC, Rowe JB, Rullmann M, Salman Y, Sarazin M, Saykin AJ, Schneider JA, Schöll M, Schott JM, Seo SW, Serrano GE, Shcherbinin S, Shekari M, Skoog I, Smith R, Sperling RA, Spruyt L, Stomrud E, Strandberg O, Therriault J, Xie F, Vandenberghe R, Villemagne VL, Villeneuve S, Visser PJ, Vossler H, Young CB, Groot C, Hansson O. Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex. Nat Neurosci. 2025 Jul 16. doi: 10.1038/s41593-025-02000-6. Epub ahead of print. PMID: 40670684.
