Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3.

Background: The regulatory role of the apolipoprotein E (APOE) ε4 allele in the clinical manifestations of spinocerebellar ataxia type 3 (SCA3) remains unclear. This study aimed to evaluate the impact of the APOE ε4 allele on cognitive and motor functions in SCA3 patients.

Methods: This study included 281 unrelated SCA3 patients and 182 controls. APOE genotypes were analyzed using PCR amplification combined with Sanger sequencing. Additionally, 96 SCA3 patients were prospectively recruited for neuropsychological and motor function assessments. Neuropsychological phenotypes were evaluated using the modified Chinese version of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). Motor function was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS).

Results: The frequency of the APOE ε4 allele was increased in SCA3 patients compared to the control group. The APOE ε4 allele was associated with better performance in language and visual memory, but also with more severe speech disturbances in SCA3 patients. Furthermore, in SCA3, the expanded CAG repeat length was correlated with poorer language memory performance and slower information processing speed, as well as more severe gait disturbances, fast alternating hand movements, speech disturbance, and oculomotor disorders.

Conclusions: The APOE ε4 allele may serve as a disease-modifying factor in SCA3, influencing both cognitive and motor functions.