The apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). This study aimed to investigate abnormality of white matter integrity and its relationship to cognitive impairments in Chinese non-demented elderly with and without the ɛ4 allele. We assessed cognitive differences using a series of neuropsychological tests and assessed white matter integrity using tract-based spatial statistics to measure mean diffusivity and fractional anisotropy. We determined that there were no statistically significant group differences in any neuropsychological measures. However, APOEɛ4 carriers without cognitive decline exhibited widespread disruption of the white matter tracts in several areas, including the cingulum, fornix, corpus callosum, and corona radiate. Furthermore, a correlation analysis in ɛ4 carriers indicated that disruption of the right fornix stria terminalis and the genu of the corpus callosum were positively associated with cognitive impairment, including memory, executive function, spatial processing, attention, and language. The present study reveals the deleterious effects of the ɛ4 allele on white matter, and this damage may potentially serve as a biomarker in preclinical investigations. Our promising results encourage further investigation using a multidimensional longitudinal approach with larger samples.
Keywords: APOE ɛ4 allele; Alzheimer’s disease; cognition; diffusion tensor imaging; tract-based spatial statistics; white matter.