Objective: To assess the frequency of APOE alleles and their association with clinical course of Colony Stimulating Factor 1 Receptor-Related Disorder (CSF1R-RD).

Background: CSF1R-RD is a rare, hereditary, rapidly progressing neurodegenerative disorder linked to variants in the CSF1R gene. It manifests with cognitive symptoms and movement disorders. The clinical presentation varies even among patients with the same pathogenic variant, and no genotype-phenotype correlation was identified to this day. It is suspected that some other genetic and environmental factors might influence the course of CSF1R-RD. APOE polymorphism is a known risk factor for Alzheimer’s disease and has been shown to influence the course of other neurodegenerative disorders, such as Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington’s disease.

Method: Blood samples from 55 patients with CSF1R-RD were evaluated for APOE polymorphism. Data on age of onset, disease duration, age of death, and clinical symptoms were collected from 24 deceased patients (13 females [54.2%] and 11 males [45.8%]) within this cohort. A comparative analysis was then performed between carriers of individual APOE alleles

Results: The most frequent APOE allele was APOE3 (77.9%), followed by APOE4 (13.7%) and APOE2 (7.3%). The frequency was like that in the general population. Among the 24 deceased CSF1R-RD patients, 7 carried an APOE4 allele. Individuals with the APOE4 allele had an earlier age of onset (37.9 [23.3, 46.0] years vs. 50.3 [43.4, 58.0] years, p=0.0438) and age of death (41.1 [40.7, 49.8] years vs. 57.5 [49.6, 67.4] years). There were no statistically significant differences in disease duration, gender distribution, or main clinical phenotype between the two groups.

Conclusion: The frequency of APOE alleles in CSF1R-RD is similar to that in the general population. The presence of the APOE4 allele is associated with an earlier symptoms’ onset and death in CSF1R-RD. APOE polymorphism might be an important modifying factor of course of CSF1R-RD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploring-the-association-of-apoe-polymorphism-and-the-clinical-course-of-csf1r-related-disorder/