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REVIEW article

Front. Neurosci.
Sec. Neurodegeneration
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1515374

The Role of Apolipoprotein E4 on Cognitive Impairment In Parkinson's Disease and Parkinsonisms

Provisionally accepted
Angenelle Eve Rosal Angenelle Eve Rosal 1,2*Sarah L Martin Sarah L Martin 1Antonio P Strafella Antonio P Strafella 1,2,3*
  • 1 Brain Imaging Health Centre, The Centre for Addiction and Mental Health, Toronto, Canada
  • 2 Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 3 Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Division of Neurology, Krembil Neuroscience Centre (KNC), Toronto Western Hospital, Toronto, Ontario, Canada

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

    Cognitive impairment is a prevalent non-motor symptom of Parkinson’s disease (PD), increasing the risk of dementia as the disease progresses. Despite its clinical significance, the aetiology of cognitive impairment in PD remains unclear. Apolipoprotein E4 (APOE4), a well-known genetic risk factor of Alzheimer’s disease, has been studied for its potential role in PD-related cognitive impairment. However, findings have been conflicting and thus inconclusive, highlighting a need to critically evaluate the current research. Several studies using neuroimaging modalities have explored the brains of individuals with PD and atypical parkinsonian disorders who have APOE4. Some of these studies have identified distinct neuropathological changes that have been previously reported to be associated with cognitive impairments in those with Parkinsonisms. Here, we review the role of APOE4 on cognitive impairment in PD and atypical Parkinsonisms using neuroimaging evidence. We will examine how APOE4 may contribute to pathological changes within the brain and its association with cognitive impairment.

    Keywords: Apolipoprotein E4, parkinsonism, DLB, cognitive decline, Neuroimaging, Parkinson's Disease'

    Received: 22 Oct 2024; Accepted: 03 Feb 2025.

    Copyright: © 2025 Rosal, Martin and Strafella. 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:
    Angenelle Eve Rosal, Brain Imaging Health Centre, The Centre for Addiction and Mental Health, Toronto, Canada
    Antonio P Strafella, Brain Imaging Health Centre, The Centre for Addiction and Mental Health, Toronto, Canada

    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.