The association between apolipoprotein ε4- <i>TOMM40’</i> 523 haplotypes and multiple system atrophy

Objectives: Accumulating evidence has increasingly indicated that apolipoprotein E ( APOE ) or TOMM40 poly-T genotypes are likely to be involved in the pathogenesis of several neurodegenerative disorders, rather than being exclusively associated with Alzheimer’s disease (AD), which was their initial and primary linked condition. This expanding understanding of their potential broader role has sparked growing interest in exploring their involvement across a wider spectrum of neurodegenerative conditions. Given the substantial overlap in multiple clinical manifestations between synucleinopathies and AD – such as shared features such as cognitive decline, motor impairments, and certain neuropsychiatric symptoms – we designed and conducted this case–control study. The specific aim was to investigate whether there exists a genetic association between APOE ε4- TOMM40 ’523 haplotypes and multiple system atrophy (MSA) within Chinese Han cohorts, thereby contributing to the understanding of MSA’s genetic underpinnings. Materials and Methods: We systematically genotyped APOE and TOMM40 ‘523 variants in a well-characterized cohort comprising 200 patients diagnosed with MSA, 66 patients with Parkinson’s disease (PD), and 320 healthy controls (HCs). All participants were carefully selected to ensure the reliability and representativeness of the study population. Results: Our analyses revealed no statistically significant differences in the distribution patterns of APOE ε4- TOMM40 ’523 haplotypes among the MSA patients, PD patients, and HCs. Furthermore, no significant correlations were observed between the ε4-’523L haplotype and key clinical parameters in MSA patients, including age at onset and disease severity scores assessed by standardized scales. Conclusion: Taken together, the findings of our study suggest that the APOE ε4- TOMM40 ’523L haplotype may not play a substantial role in the pathogenesis of MSA, providing valuable insights into the genetic factors that may or may not contribute to this complex neurodegenerative disorder.