Apolipoprotein E4, Amyloid, and Cognition in Alzheimer’s and Lewy Body Disease

Background: The role of APOE4 in the risk of Alzheimer’s disease, Lewy body disease, and their mixed diseases have not been evaluated in antemortem patients. Also, the APOE4 effect on β-amyloid deposition and cognition, with consideration of both Alzheimer’s and Lewy body diseases, remains unclear. We aimed to determine the APOE4 effects on the risk of Alzheimer’s disease, Lewy body disease, and their mixed diseases, as well as on β-amyloid deposition and cognition after adjusting for the effect of Alzheimer’s disease and Lewy body disease.Methods: Based on clinical features and 18F-Florbetaben and dopamine transporter PET, we recruited 126 controls, 90 patients with typical Alzheimer’s disease (57 pure Alzheimer’s disease, 32 Lewy body variant of Alzheimer’s disease), 77 with typical Lewy body disease (56 pure Lewy body disease, 21 dementia with Lewy bodies with amyloid deposition), and 42 with typical Alzheimer’s disease/dementia with Lewy bodies. We used logistic regression analysis to investigate the effect of APOE4 on the risk of each disease and general linear models to investigate the independent and interaction effects of APOE4, Alzheimer’s disease, and Lewy body disease on β-amyloid deposition and cognition. Results: APOE4 was associated with increased risks of all disease subtypes except pure Lewy body disease. APOE4 was associated with increased frontal β-amyloid burden, typical Alzheimer’s disease was associated with increased β-amyloid burden in all lobar regions, and typical Lewy body disease interacted with APOE4 to increase the occipital β-amyloid burden. The interaction of APOE4 and typical Alzheimer’s disease was associated with more severe memory dysfunction, while that of APOE4 and typical Lewy body disease was associated with poorer Clinical Dementia Rating Sum of Boxes. Conclusions: Our findings suggest that the APOE4 effect on disease risk is dependent on β-amyloid deposition and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis; however, APOE4 further interacts with typical Lewy body disease to induce worse general cognition and higher occipital β-amyloid deposition and it interacts with typical Alzheimer’s disease to decrease memory function. This study highlights the possible interaction of β-amyloid and Lewy body pathologies converging in the occipital cortex through the APOE4 effect.