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In this narrative review, we delved into the intricate interplay between <i>Apolipoprotein E (APOE)</i> alleles (typically associated with Alzheimer’s disease—AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of <i>APOE4</i> on LB pathology were summarized. We found robust evidence that <i>APOE4</i> carriage constitutes a risk factor for PDD—APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that <i>APOE4</i> copies confer an increased hazard towards DLB, as well. Again <i>APOE2</i> and <i>APOE3</i> appear unrelated to the risk of conversion. Of note, in individuals with DLB <i>APOE4</i>, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; <i>APOE</i>-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the <i>APOE</i> gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive–neuropsychiatric- motor-, and sleep-related manifestations) between <i>APOE</i> alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.