Skip to main content

REVIEW article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1535280

Multi-Functional Role of Apolipoprotein E in Neurodegenerative Diseases

Provisionally accepted
Sadequl Islam Sadequl Islam 1ARSHAD NOORANI ARSHAD NOORANI 2YANG SUN YANG SUN 1Makoto Michikawa Makoto Michikawa 3Kun Zou Kun Zou 1*
  • 1 Department of Neuro-oncology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
  • 2 University of Kansas, Lawrence, United States
  • 3 Department of Geriatric Medicine, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan

The final, formatted version of the article will be published soon.

    Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer's disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common ApoEε3 allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid β-protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE's diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE's influence in other neurodegenerative diseases like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington's disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases.

    Keywords: Apolipoprotein E, Alzheimer's disease, amyloid-β (Aβ), Parkinson's disease, Amyotrophic Lateral Sclerosis, neurodegenerative diseases. 1. Introduction

    Received: 27 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Islam, NOORANI, SUN, Michikawa and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kun Zou, Department of Neuro-oncology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.