Abstract

Apolipoprotein E (APOE) increases the risk for Alzheimer’s disease (ε4 allele) and cerebral amyloid angiopathy (ε2 and ε4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium. Compared with APOE ε3/ε3, WMHV was increased in APOE ε2 (P=0.02) but not APOE ε4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE ε2 on WMHV caused by pure SVD.