Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

Area of Science:

• Neurogenetics
• Neurodegenerative Diseases
• Molecular Biology

Background:

• The Apolipoprotein E (APOE) gene, particularly the APOE4 allele, is a significant risk factor for Alzheimer's disease (AD).
• Alpha-synucleinopathies (aS-pathies) encompass Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA).
• The relationship between APOE alleles and aS-pathies requires further elucidation.

Purpose of the Study:

• To review and synthesize current evidence on the interplay between APOE alleles and aS-pathies.
• To summarize the effects of APOE alleles on Lewy body pathology and disease phenotypes.
• To identify gaps in the literature and propose future research directions.

Main Methods:

• Narrative review of in-vitro, animal, and human-based studies.
• Analysis of existing literature on APOE allele associations with PDD, DLB, PD, and MSA.
• Examination of phenotypic associations between APOE alleles and clinical manifestations.

Main Results:

• APOE4 carriage is a risk factor for PDD and DLB, while APOE2 and APOE3 appear unrelated to PDD risk.
• APOE4 prevalence in DLB is intermediate between AD and PDD.
• APOE-PD associations are ethnicity-dependent; no association was found between APOE and MSA.

Conclusions:

• APOE genotype significantly influences the risk and potentially the phenotype of specific alpha-synucleinopathies, particularly DLB and PDD.
• APOE4 is a risk factor for DLB and PDD, with varying prevalence across neurodegenerative diseases.
• Further research is needed to clarify APOE's role in PD and other aS-pathies, considering ethnic variations and specific phenotypic impacts.