Influence of APOE on the Alzheimer’s disease polygenic risk scores based on hippocampal subfield volumes

Abstract

AbstractBackgroundNumerous studies have shown the association between Alzheimer’s disease, hippocampal subfield volume atrophy, and the role of APOE. In our previous study, we showed the differential atrophy in the hippocampal subfield volumes (HSV) identified using Alzheimer’s disease polygenic risk scores (AD PGRS). Here, we evaluate the influence of the APOE 𝛆4 on the AD PGRS of the HSV.MethodWe calculated the AD PGRS for HSV atrophy in 1,086 individuals (319 cognitively normal (CN), 591 mild cognitively impaired (MCI), and 176 Alzheimer’s disease dementia (ADD)). We then stratified the samples based on the APOE 𝛆4 carriers and non‐carriers. We studied the AD PGRS for the HSV for the left‐right hemispheres.ResultThe analysis was performed for the left and right hemispheres separately. The effects of APOE 𝛆4 were larger on the left hemisphere than on the right hemisphere. The effects of the APOE 𝛆4 were severe on most of the subfield volumes. Although, certain subfield volumes showed larger effects for 𝛆4 non‐carriers and certain subfield volumes showed no effect between 𝛆4 carriers and non‐carriers.ConclusionThe APOE 𝛆4 carriers showed a higher AD PGRS for hippocampal subfield volume atrophy than the APOE 𝛆4 non‐carriers. The AD PGRS and the APOE 𝛆4 showed the differential risk for the subfield volumes bilaterally. These risk scores can be used in preclinical Alzheimer’s risk modeling. We also hypothesize that hippocampal subfield volume atrophy occurs in both normal and pathological aging. However, atrophy is intense in pathological aging due to the underlying processes and the functioning of the risk genes. A clear understanding of this will enhance the specificity and sensitivity for the early diagnosis of Alzheimer’s disease.