The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms

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 etiology of cognitive impairment in PD remains unclear. Apolipoprotein E4 (APOE4), a well-known genetic risk factor of...

Full description

Saved in:
Bibliographic Details
Main Authors: Angenelle Eve Rosal, Sarah L. Martin, Antonio P. Strafella
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1515374/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850025473515454464
author Angenelle Eve Rosal
Angenelle Eve Rosal
Sarah L. Martin
Sarah L. Martin
Antonio P. Strafella
Antonio P. Strafella
Antonio P. Strafella
author_facet Angenelle Eve Rosal
Angenelle Eve Rosal
Sarah L. Martin
Sarah L. Martin
Antonio P. Strafella
Antonio P. Strafella
Antonio P. Strafella
author_sort Angenelle Eve Rosal
collection DOAJ
description 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 etiology 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.
format Article
id doaj-art-e471fe0e572f49ac935ae8da70f8e518
institution DOAJ
issn 1662-453X
language English
publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj-art-e471fe0e572f49ac935ae8da70f8e5182025-08-20T03:00:50ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-02-011910.3389/fnins.2025.15153741515374The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and ParkinsonismsAngenelle Eve Rosal0Angenelle Eve Rosal1Sarah L. Martin2Sarah L. Martin3Antonio P. Strafella4Antonio P. Strafella5Antonio P. Strafella6Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, CanadaInstitute of Medical Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, CanadaBrain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, CanadaTranslation and Computational Neurosciences Unit (TCNU), Faculty of Health and Education, Manchester Metropolitan University, Manchester, United KingdomBrain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, CanadaInstitute of Medical Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, CanadaEdmond J. Safra Parkinson Disease Program, Neurology Division, Toronto Western Hospital and Krembil Brain Institute, University Health Network, University of Toronto, Toronto, ON, CanadaCognitive 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 etiology 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.https://www.frontiersin.org/articles/10.3389/fnins.2025.1515374/fullApolipoprotein E4ParkinsonismDLBcognitive impairmentneuroimagingParkinson’s disease
spellingShingle Angenelle Eve Rosal
Angenelle Eve Rosal
Sarah L. Martin
Sarah L. Martin
Antonio P. Strafella
Antonio P. Strafella
Antonio P. Strafella
The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
Frontiers in Neuroscience
Apolipoprotein E4
Parkinsonism
DLB
cognitive impairment
neuroimaging
Parkinson’s disease
title The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
title_full The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
title_fullStr The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
title_full_unstemmed The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
title_short The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
title_sort role of apolipoprotein e4 on cognitive impairment in parkinson s disease and parkinsonisms
topic Apolipoprotein E4
Parkinsonism
DLB
cognitive impairment
neuroimaging
Parkinson’s disease
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1515374/full
work_keys_str_mv AT angenelleeverosal theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT angenelleeverosal theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT sarahlmartin theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT sarahlmartin theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella theroleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT angenelleeverosal roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT angenelleeverosal roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT sarahlmartin roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT sarahlmartin roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms
AT antoniopstrafella roleofapolipoproteine4oncognitiveimpairmentinparkinsonsdiseaseandparkinsonisms