Tau‐Atrophy Variability Reveals Phenotypic Heterogeneity in Alzheimer's Disease

• DOI: 10.1002/ana.26233
• Publication Date: 2021-10-09T07:08:16Z
• Authors: Sandhitsu R. Das; Xueying Lyu; Michael Tran Duong; Long Xie; Lauren McCollum; Robin de Flores; Michael DiCalogero; David J. Irwin; Bradford C. Dicke...; Ilya M. Nasrallah; Paul A. Yushkevich; David A. Wolk
• Keywords: Pittsburgh compound B

Tau neurofibrillary tangles (T) are the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in Alzheimer's disease (AD). However, there is substantial variability T-N relationship - manifested higher or lower atrophy than expected for level tau a given brain region. The goal this study was to determine if region-based quantitation allows identification underlying modulatory factors, including polypathology.Cortical thickness 18 F-Flortaucipir SUVR were computed 104 gray matter regions from cohort cognitively-impaired, amyloid-positive (A+) individuals. Region-specific residuals robust linear fit between cortical as surrogate mismatch. A summary mismatch metric defined using correlated with demographic imaging-based partition into data-driven subgroups.The factors such age burden white hyperintensity lesions. Data-driven subgroups based on clustering appear represent different biologically relevant phenotypes, groups showing distinct spatial patterns expected.These data support notion that measure deviation normative across individuals AD continuum captures due multiple can reveal which validated, may help identify possible contributors addition tau, ultimately be useful selection clinical trials. ANN NEUROL 2021;90:751-762.