Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease

Jin Ho Jung,Seun Jeon,Kyoungwon Baik,Yang Hyun Lee,Seok Jong Chung,Han Soo Yoo,Seong Ho Jeong,Young H Sohn,Phil Hyu Lee,Byoung Seok Ye

doi:10.1016/j.neurobiolaging.2021.06.004

Abstract

The role of apolipoprotein E4 (APOE4) in the risk of Alzheimer's disease (AD) and Lewy body disease (LBD), and their relationship with β-amyloid deposition and cognitive dysfunction, remain unclear. Using amyloid and dopamine transporter imaging, we enrolled 126 controls and 208 patients with typical AD (pure AD and Lewy body variant of AD), AD with dementia with Lewy bodies, or typical LBD (dementia with Lewy bodies with amyloid deposition and pure LBD). APOE4 was associated with an increased risk of all disease subtypes except pure LBD. APOE4 was associated with increased frontal β-amyloid burden, and typical LBD was associated with increased occipital β-amyloid levels through its interaction with APOE4. APOE4 was associated with deteriorated general cognition and memory dysfunction via its interaction with typical LBD and AD, respectively. In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.

Highlights

The role of apolipoprotein E4 (APOE4) in the risk of Alzheimer’s disease, Lewy body disease, and their mixed diseases have not been evaluated in antemortem patients
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; 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

Summary

Introduction

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. 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. Advances in amyloid and dopamine transporter imaging have allowed the in vivo diagnosis of AD [13], LBD [14], and their mixed diseases [15]; the role of APOE4 in the risk of AD and LBD, with consideration of their mixed diseases, remains unclear

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