Chen Xuanyu, Lin Kunxin, Ye Zhixian, Qiu Liangliang, Qiu Yusen, Yuan Ruying, Yu Xintong, Huang Chunyu, Cheng Bi, Lin Wei, Lai Tianmin, Chen Wanjin, Wang Ning, Gan Shirui, Su Qiuni, Fu Ying
School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
Eur J Neurol. 2025 Jan;32(1):e70017. doi: 10.1111/ene.70017.
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.
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).
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.
The APOE ε4 allele may serve as a disease-modifying factor in SCA3, influencing both cognitive and motor functions.
载脂蛋白E（APOE）ε4等位基因在3型脊髓小脑共济失调（SCA3）临床表现中的调节作用仍不清楚。本研究旨在评估APOE ε4等位基因对SCA3患者认知和运动功能的影响。
本研究纳入了281例无亲缘关系的SCA3患者和182例对照。采用聚合酶链反应（PCR）扩增结合桑格测序分析APOE基因型。此外，前瞻性招募了96例SCA3患者进行神经心理学和运动功能评估。使用改良中文版的多发性硬化症认知功能简易评估量表（MACFIMS）评估神经心理学表型。使用共济失调评估与评分量表（SARA）和国际合作共济失调评分量表（ICARS）评估运动功能。
与对照组相比，SCA3患者中APOE ε4等位基因的频率增加。APOE ε4等位基因与SCA3患者更好的语言和视觉记忆表现相关，但也与更严重的言语障碍相关。此外，在SCA3中，扩展的CAG重复长度与较差的语言记忆表现、较慢的信息处理速度以及更严重的步态障碍、快速交替手部运动、言语障碍和眼球运动障碍相关。
APOE ε4等位基因可能作为SCA3的疾病修饰因子，影响认知和运动功能。
