Trompeta Clara, Gasca-Salas Carmen, Rodríguez-Rojas Rafael, Fernández-Rodríguez Beatriz, Clarimón Jordi, García-Cañamaque Lina, Guida Pasqualina, Hernández-Fernández Frida, Sánchez-Juan Pascual, Olazarán Javier, Vela-Desojo Lydia
HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain; Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain; PhD Program in Health Sciences, University of Alcala de Henares, Alcala de Henares, Spain.
HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain; Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain; University CEU-San Pablo, Madrid, Spain; Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain.
J Neurol Sci. 2025 Jun 15;473:123510. doi: 10.1016/j.jns.2025.123510. Epub 2025 Apr 17.
Cognitive impairment is a common non-motor manifestation in Parkinson's disease (PD). Amyloidosis seems to accelerate the onset of dementia in PD. The Apolipoprotein (APOE) ε4 genotype is linked to amyloid aggregation and has been suggested to be a candidate for development of PD dementia, while other APOE alleles have been less investigated.
Forty-eight non-demented PD patients were included (ε2/ε3 carriers: n = 8; ε3/ε3 carriers: n = 35; and ε3/ε4 carriers: n = 5). Patients underwent APOE genotyping, a neuropsychological exam and a [18F]-Flutemetamol PET. Statistical Parametric Mapping 12 was used to analyze regional amyloid differences by APOE genotypes. Cognitive assessment was re-administered after follow-up.
APOE ε3/ε4 carriers showed significant amyloid load in left middle occipital areas in comparison with APOE ε3/ε3, whereas APOE ε3/ε4 exhibited several areas of amyloid accumulation in comparison with APOE ε2/ε3 that disappeared after family-wise error cluster level correction, but which hold in nonparametric analyses. No amyloid load differences were found between APOE ε2/ε3 and APOE ε3/ε3. The frequency of progression of cognitive decline was 80 % in ε3/ε4, 50 % in ε2/ε3, and 22.86 % in ε3/ε3 carriers.
This compared regional amyloid deposition and cognitive evolution among APOE genotypes. Our preliminary findings suggest an association between APOE ε4 and amyloid burden in posterior cortical areas in non-demented PD and a tendency to a higher frequency of cognitive decline. Larger studies should explore cognition and amyloid burden in APOE ε2 carriers.
认知障碍是帕金森病（PD）常见的非运动症状。淀粉样变性似乎会加速PD患者痴呆的发病。载脂蛋白（APOE）ε4基因型与淀粉样蛋白聚集有关，被认为是PD痴呆发生的一个候选因素，而其他APOE等位基因的研究较少。
纳入48例非痴呆PD患者（ε2/ε3携带者：n = 8；ε3/ε3携带者：n = 35；ε3/ε4携带者：n = 5）。患者接受APOE基因分型、神经心理学检查和[18F] - 氟代甲磺酸去甲肾上腺素PET检查。使用统计参数映射12分析不同APOE基因型的区域淀粉样蛋白差异。随访后重新进行认知评估。
与APOE ε3/ε3相比，APOE ε3/ε4携带者左侧枕中区域淀粉样蛋白负荷显著增加；与APOE ε2/ε3相比，APOE ε3/ε4表现出多个淀粉样蛋白聚集区域，经家族性错误聚类水平校正后这些区域消失，但在非参数分析中仍然存在。APOE ε2/ε3和APOE ε3/ε3之间未发现淀粉样蛋白负荷差异。ε3/ε4携带者认知功能下降进展的频率为80%，ε2/ε3为50%，ε3/ε3为22.86%。
本研究比较了不同APOE基因型之间的区域淀粉样蛋白沉积和认知演变。我们的初步研究结果表明，在非痴呆PD患者中，APOE ε4与后皮质区域的淀粉样蛋白负荷有关，且认知功能下降的频率有升高趋势。更大规模的研究应探讨APOE ε2携带者的认知和淀粉样蛋白负荷情况。
