APOE ε4-associated heterogeneity of neuroimaging biomarkers across the Alzheimer's disease continuum

INTRODUCTIONWhile the role of apolipoprotein E (APOE) epsilon 4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE epsilon 4 carriers versus non-carriers. METHODSTo help elucidate these differences, we performed a broad analysis comparing the regional levels of six different neuroimaging biomarkers in the brains of APOE epsilon 4 carriers versus non-carriers who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTSWe observed significant APOE epsilon 4-associated heterogeneity in regional amyloid beta deposition, tau accumulation, glucose uptake, brain volume, cerebral blood flow, and white matter hyperintensities within each AD diagnostic group. We also observed important APOE epsilon 4-associated differences in cognitively unimpaired individuals who converted to mild cognitive impairment/AD versus those who did not convert. DISCUSSIONThis observed heterogeneity in neuroimaging biomarkers between APOE epsilon 4 carriers versus non-carriers may have important implications regarding the prevention, diagnosis, and treatment of AD in different subpopulations. Highlights An extensive study was performed on the apolipoprotein E (APOE) epsilon 4-associated heterogeneity in neuroimaging biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Robust APOE epsilon 4-associated increases in amyloid beta (A beta) deposition throughout the brain, in every diagnostic group, were observed. APOE epsilon 4-associated increases in tau pathology, decreases in glucose uptake, and increases in brain atrophy, which expand in regional scope and magnitude with disease progression, were observed. Significant sex- and age-related differences in APOE epsilon 4-associated neuroimaging biomarker heterogeneity, with overall increases in pathological presentation in female APOE epsilon 4 carriers, were observed. Regional differences in A beta deposition, tau accumulation, glucose uptake, ventricle size, and white matter hyperintensities were observed in cognitively normal participants who converted to mild cognitive impairment/Alzheimer's disease, which may hold potential predictive value.