APOE ε4 allele advances the age-dependent decline of amyloid β clearance in the human cortex

Introduction Our previous study indicated that the pericapillary clearance of amyloid β (Aβ) declines with age in APOE 3/3 subjects. Here, we examine whether the APOE ε 4 allele has an impact on this age-related decline. Methods We examined 69 autopsy brains of APOE ε 3/ ε 4 or APOE ε 3/ ε 3 individuals (30-65 years) for the immunohistochemical localization of intracellular, extracellular, and pericapillary Aβ in the cerebral cortex. Results In APOE ε 3/ ε 4 individuals, the percentage of Aβ positive pericapillary spaces began to decrease (p=0.030), and the number of extracellular Aβ particles increased in the early 30s (p=0.0008). Those average values were significantly lower (p<0.0001) and higher (p<0.0001), respectively, compared to APOE ε 3/ ε 3 individuals. Discussion Our observations indicate that APOE ε 4 allele advances by one decade at the onset of age-related decline in Aβ glymphatic clearance. This finding supports early clinical intervention and stratification by APOE genotype to prevent Aβ deposition and AD progression. ### Competing Interest Statement The authors have declared no competing interest.