Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

In this narrative review, we delved into the intricate interplay between 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 on LB pathology were summarized. We found robust evidence that carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that copies confer an increased hazard towards DLB, as well. Again and appear unrelated to the risk of conversion. Of note, in individuals with DLB , carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; -PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.