Objective:

Background:

APOE e4 is a known genetic factor affecting Alzheimer’s disease (AD) risk. Alzheimer’s pathology is commonly observed in DLB and is associated with worse functional cognition and faster memory decline. It remains uncertain whether APOE e4 independently contributes to Lewy body pathology, and whether Alzheimer’s co-pathology contributes to the core clinical features of DLB.

Design/Methods:

A total of 38,414 participants, composed of 1,170 DLB, 1,032 Parkinson's disease (PD), 17,416 AD and 18,796 controls (CN), were included in this study. Logistic regression was applied to examine the relation between neuropathology and APOE genotype, and to assess the relation between APOE genetic risk score and the four core clinical features.

Results:

APOE e4 was associated with more severe Lewy body pathology in participants with not or low AD neuropathologic change (OR: 1.39, 95%CI: 1.01, 1.94, p = 0.049). Two-thirds of DLB participants developed fluctuating cognition, visual hallucinations, or RBD, more than in PD, AD, and CN groups. 86.9% of DLB participants developed parkinsonism, which was significantly higher than in AD and CN groups. The risk of developing fluctuating cognition decreased with increased APOE genetic risk score (OR: 0.72, 95%CI: 0.53, 0.97, p = 0.031). Similar patterns were observed for RBD and parkinsonism. In contrast, the risk of developing visual hallucinations increased with increased APOE genetic risk score (OR: 1.16, 95%CI: 1.12, 1.20, p < 0.001). 

Conclusions:

An association appears to exist between APOE e4 and Lewy body pathology that is independent of the severity of Alzheimer’s pathology. The core clinical features of LBD are sensitive to APOE e4 haplotype.