Citations 2
Characterizing amyloid and tau positron emission tomography‐based stages across the clinical continuum
Cody, Karly Alex , Sokołowski, Andrzej , Johns, Emily , Guerra, Lucah Medina, Dumitrescu, Logan, Durant, Alaina, Sathe, Aditi, Koran, Mary Ellen I. , Mez, Jesse, Saykin, Andrew J., Toga, Arthur W., Cuccaro, M. L., Tosun, Duygu, Insel, Philip S., Johnson, Sterling C., Harrison, Theresa, Hohman, Timothy J., Mormino, Elizabeth C., Cody, Karly A , Sokołowski, Andrzej, Winer, Joseph R. , Young, Christina B. , Younes, Kyan , Dumitrescu, Logan , Archer, Derek B. , Durant, Alaina, Mez, Jesse , Saykin, Andrew J. , Toga, Arthur W. , Cuccaro, Michael L. , Insel, Philip S. , Johnson, Sterling C. , Harrison, Theresa M. , Hohman, Timothy J. , Mormino, Elizabeth C.
Alzheimer's & Dementia | January 8, 2026 | Volume: 22 | Issue: 1 | Pages: No page available
Abstract INTRODUCTION We standardized positron emission tomography (PET) data across multiple cohorts and tracers to characterize the frequency of amyloid and tau PET severity along the clinical continuum. METHODS Clinical stage was defined using cohort‐specific criteria and included cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia. Amyloid severity was staged using Centiloids (CL). Tau severity was staged using a hierarchical Braak‐based schema. The cumulative probabilities of PET‐based stages were estimated using ordinal logistic regressions. RESULTS Among 10,396 individuals (mean [standard deviation] age: 71.9 [7.1] years), amyloid levels ≥ 25 CL increased with age among CU and MCI, while amyloid levels ≥ 100 CL were most common in dementia. In 3295 with tau PET, tau severity increased with amyloid and clinical stage and showed complex associations with age. Within each clinical stage, the full spectrum of amyloid and tau PET severity was observed. DISCUSSION PET‐based staging revealed heterogeneous amyloid and tau burden along the clinical continuum. Highlights PET‐based staging is feasible across multiple cohorts and PET tracers. There is heterogeneity in amyloid and tau severity across the clinical spectrum. The frequency of amyloid and tau PET severity increased with clinical severity. The likelihood of tau PET severity differed by age, amyloid, and clinical severity.
APOE, ABCA7 , and RASGEF1C are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images
Castellano, Tonnar , Wang, Ting Chen, Nolan, Emma , Wu, Yiyang , Clifton, Michelle, Janve, Vaibhav A. , Durant, Alaina, Regelson, Alexis, Cody, Karly Alex , Jagust, William, Albert, Marilyn , Resnick, Susan M. , Mayeux, Richard, Initiative, Alzheimer's Disease Neuroimaging, Bennett, David A. , Jager, Philip L. De , Mormino, Elizabeth C. , Koran, Mary Ellen I. , Wang, Ting‐Chen , Bennett, David A. , Koran, Mary Ellen , Cody, Karly A , Wang, Ting Chen, Zhang, Mengna , Harrison, Theresa M. , Engelman, Corinne D. , Johnson, Sterling C. , Sperling, Reisa Anne , Bilgel, Murat , Saykin, Andrew J. , Vardarajan, Badri Narayan , Mayeux, Richard , Initiative, Alzheimer's Disease Neuroimaging, Betthauser, Tobey J. , Schneider, Julie A. , Menon, Vilas , Tosun, Duygu , Archer, Derek B. , Dumitrescu, Logan , Hohman, Timothy J.
Alzheimer's & Dementia | December 13, 2025 | Volume: 21 | Issue: 12 | Pages: No page available
Abstract INTRODUCTION New methods estimate amyloid positivity onset age (EAOA) from amyloid positron emission tomography (PET). We explore the genetics of EAOA to identify molecular factors underlying the earliest Alzheimer's disease (AD) changes. METHODS Harmonized amyloid PET data from 4216 participants were used in genome‐wide survival, tissue‐specific gene expression, and genetic covariance analyses of EAOA. RESULTS Variants in apolipoprotein E ( APOE ), ABCA7 , and RASGEF1C associated with earlier EAOA. APOE ε4/ε4 and ε3/ε4 converted 6.3 and 5 years earlier than ε3/ε3, respectively. ε2 was protective against earlier EAOA. rs4147929, an expression quantitative trait locus for ABCA7 , associated with a 4 year earlier EAOA. This variant was associated with lower brain expression of ABCA7 , which was associated with increased amyloid pathology at autopsy. Multiple immune‐related diseases shared genetic covariance with EAOA. DISCUSSION APOE , ABCA7 , and RASGEF1C associated with earlier EAOA, with supporting evidence from tissue‐specific expression analyses, offering insights into intervenable targets at early stages of AD. Highlights Novel methods estimate how long ago a patient converted to amyloid positivity. Estimating this amyloid clock allows us to determine the onset of the earliest Alzheimer's disease changes. We evaluated what genes influence when someone converts to amyloid positivity. Apolipoprotein E ( APOE ) , ABCA7 , and RASGEF1C associated with earlier age of amyloid positivity. Genetic results were supported by tissue‐specific expression analyses.