アポリポプロテインE多型とコロニー刺激因子1受容体関連障害における発症年齢および神経病理との関連

Colony stimulating factor 1 receptor-related disorder (CSF1R-RD) is a rare, rapidly progressive neurodegenerative disease with significant clinical heterogeneity. Apolipoprotein E (ApoE) polymorphism, known to modulate microglial function and influence neurodegeneration, may act as a genetic modifier in CSF1R-RD.

The objectives were to evaluate the distribution of ApoE alleles in CSF1R-RD and assess their association with clinical and neuropathological features.

ApoE genotyping was performed in 55 individuals with CSF1R-RD. Clinical data from 25 deceased patients were analyzed based on ApoE genotype. Neuropathological evaluation was conducted on brain tissue from 14 patients, with semiquantitative scoring of white matter pathology and microglial burden. Statistical comparisons were made between carriers and noncarriers of the ApoE4 allele.

ApoE allele frequencies in CSF1R-RD mirrored those of the general population (ε2: 7.3%, ε3: 79.1%, ε4: 13.6%). However, ApoE4 carriers exhibited significantly earlier symptom onset (median: 37.9 vs. 50.3 years, p = 0.0123) and death (median: 41.1 vs. 55.2 years, p = 0.0072). Neuropathological analysis revealed more severe white matter involvement and reduced microglial preservation in ApoE4 carriers (p = 0.034).

Although ApoE allele distribution does not differ from the general population, the presence of the ApoE4 allele may influence the clinical trajectory and white matter pathology in CSF1R-RD. These findings suggest that ApoE polymorphism is a potential modifier of disease course and should be considered in therapeutic planning and future research. © 2026 International Parkinson and Movement Disorder Society.