APOE ε4 influences medial temporalatrophy and tau deposition in atypical Alzheimer's disease

Introduction: Apolipoprotein E (APOE) epsilon 4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD. Methods: An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE epsilon 4 on cross-sectional and longitudinal regional metrics. Results: At baseline, APOE epsilon 4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE epsilon 4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus. Discussion: APOE epsilon 4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.