Hippocampal volume and genetic risk for Alzheimer’s disease


  • Endophenotypic manifestations of polygenic risk for Alzheimer’s disease (AD) are not confined to older age or clinical cohorts but seen across the life span in cognitively healthy individuals.

Why this matters

  • Studies have associated APOE ε4 and higher AD polygenic risk scores (PGS) with smaller hippocampal size, mainly in older adults, but there is growing evidence for continuous influence of early life factors on later cognitive function and neural mechanisms.

  • The presence of AD endophenotypic manifestations in younger, cognitively healthy individuals has important implications for early targeted therapy development that may potentially delay or halt AD disease progression and improve patient outcomes.