Apolipoprotein E4 in Alzheimer’s Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment

TL;DR

This review explores how the ApoE4 gene variant contributes to Alzheimer's disease, affecting brain barriers, lipid metabolism, and treatment responses.

Contribution

The paper integrates recent findings on ApoE4's role in AD pathology and treatment, emphasizing personalized medicine approaches.

Findings

ApoE4 is strongly linked to advanced Alzheimer's pathology and blood–brain barrier disruption.

ApoE4 influences lipid metabolism changes in Alzheimer's patients.

ApoE4 status should be considered in developing and personalizing Alzheimer's treatments.

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Among the genetic risk factors linked to AD, the Apolipoprotein E4 (ApoE4) remains the strongest. It is well known that carrying the ApoE4 isoform is associated with advanced AD pathology, blood–brain barrier (BBB) disruption, and changes in lipid metabolism. In this review, we provide an overview of the role of centrally and peripherally produced ApoE in AD. After this introduction, we focus on new findings regarding ApoE4’s effects on AD pathology and BBB function. We then discuss ApoE’s role in lipid metabolism in AD, highlighting examples of lipid changes caused by carrying the ApoE4 isoform. Next, the review explores the implications of ApoE4 isoforms for current treatments—whether they involve anti-amyloid therapy or other pharmacological agents used for AD—emphasizing the importance of personalized medicine approaches for patients with this high-risk allele. This review aims to provide an updated overview of ApoE4’s effects on AD pathology and treatment. By integrating recent discoveries, it underscores the critical need to consider ApoE4 status in both research and clinical settings to enhance therapeutic strategies and outcomes for individuals with AD.

Figures