Neuroimaging Compendium of Microglia, Amyloid, Tau, and Neurodegeneration Across Clinical Variants of Alzheimer Disease

Alzheimer disease and its clinical variants have characteristic spatial and temporal progression patterns of amyloid and tau driving symptomatology, but the distribution of microglia density, as measured by 18kDa translocator protein (TSPO) PET, is unknown. Baseline TSPO, amyloid, and tau PET as well as T1 MRI from the longitudinal imaging of microglial activation in different clinical variants of Alzheimer disease study were adjusted for age, sex, body mass index, APOE4 status, TSPO genotype, and intracranial total volume. Imaging outcomes were standardized against controls, visualized across the brain, and placed along a pseudo-longitudinal timeline using disease duration. Microglia density follows the spatial distribution of tau in amyloid-positive individuals and that of neurodegeneration in amyloid-negative individuals. The magnitude, location, and timing of elevated microglia density relative to amyloid, tau, and neurodegeneration is specific to different clinical subtypes of Alzheimer disease.