White Matter Lesion Load Increases the Risk of Low CSF Aβ42 in Apolipoprotein E-ɛ4 Carriers Attending a Memory Clinic

Abstract

White matter lesions (WMLs) are age-related manifestations of ischemic cerebrovascular disease and increase the risk for Alzheimer's disease (AD). The apolipoprotein E (ApoE) ɛ4 allele is a risk factor for late onset AD and has been related to low cerebrospinal fluid (CSF) Aβ42 levels and to cerebrovascular disease. The present study analyzed the relationship between WMLs, ApoE-ɛ4 genotype, and low CSF Aβ42. A total of 235 memory clinic attenders were stratified in 3 groups according to WML load. WMLs were rated on axial T2 magnetic resonance imaging images. Group 1 had no or only small amounts of periventricular (PV) or subcortical (SC) WMLs, WML group 2 had high amounts of PV WMLs and low amounts of SC WMLs, and WML group 3 had high amounts of both PV and SC WMLs. In each WML group, ApoE-ɛ4 genotype was used in logistic regression as a predictor for low CSF Aβ42 (cutoff≤450 ng/L). The odds ratio (OR) of having low CSF Aβ42 was significantly increased in the presence of ApoE-ɛ4 only in WML group 3 (OR 3.69, P=.009). A high WML load may interact with the ApoE-ɛ4 genotype and increase the risk for reduced CSF Aβ42 in patients attending a memory clinic.