Objective: To assess the influence of the Apolipoprotein E (APOE) gene variants on Progressive supranuclear palsy (PSP) phenotypic expression.

Background: PSP is a rare neurodegenerative disorder encompassing several phenotypes with various motor and cognitive deficits.

Method: In a cross-sectional study, we retrospectively reviewed the charts of all patients classified as PSP and re-categorized them into phenotypes using the MDS-2017 criteria. Phenotypes were divided into three subgroups: Richardson’s syndrome (PSP-RS), PSP-cortical (PSP-F +PSP-SL +PSP-CBS) and PSP-subcortical (PSP-P +PSP-PGF +PSP-PI +PSP-OM +PSP-C +PSP-PLS). Data on clinical and neuropsychological assessments were collected. Genotyping of APOE was performed using the RFLP-PCR and verified by Sanger sequencing.

Results: We included 85 PSP patients comprising 10 phenotypes classified into 28 PSP-RS, 30 PSP-cortical (17.6% PSP-CBS, 9.4% PSP-F, 8.2% PSP-SL) and 27 PSP-subcortical (14.1% PSP-P, 9.4% PSP-PI, 3.5% PSP-OM,2.4% PSP-PGF, 1.2% PSP-C, 1.2% PSP-PLS) subgroups. APOE genotypes had different frequencies across PSP subtypes. Approximately 10% of PSP patients were carriers for the homozygous form of APOE ɛ4ɛ4, and 22.6% of cases were carried one copy of APOE ɛ4 allele. However, no significant differences were noted in genotypes’ distribution across the PSP subgroups. Overall, PSP-APOEε4 carriers developed parkinsonism earlier (p=0.038), had earlier oculomotor dysfunction (p=0.052) and more altered cognitive profile. It was also associated with younger age of parkinsonism onset in PSP-RS phenotype (p=0.026). In fact, PSP-RS with APOE ɛ4 developed parkinsonian syndrome at 56 years compared to 69 years for cases without APOE ɛ4.

Conclusion: This study demonstrated the wide phenotypic spectrum of PSP among Tunisians. APOEε4 allele was associated to falls and initial oculomotor dysfunction and seemed to play a role in defining a more altered cognitive profile in PSP patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apoe-effect-on-progressive-supranuclear-palsy-phenotypes/