Role of Apolipoprotein E in the Clinical Profile of Atypical Parkinsonian Syndromes

Introduction: Atypical Parkinsonian syndromes (APS) encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). The effects of the Apolipoprotein E ( APOE ) gene on APS clinical features are controversial and understudied in several populations. We aimed to explore the influence of APOE genotype on clinical features in an APS Tunisian cohort. Methods: We included clinically diagnosed APS patients genotyped for APOE , and analyzed the clinical and APOE genotype associations. Results: A total of 328 APS patients were included, comprising 184 DLB, 58 PSP, 49 MSA, and 37 CBS. Significant differences in initial Mini-Mental State Examination and Frontal Assessment Battery scores according to APOE genotypes ( P =0.05 and 0.0048) were found. Executive dysfunction ( P =0.026) disorientation ( P =0.025), and hallucinations ( P <0.001) were more pronounced among APOE -ɛ4 carriers particularly in DLB. Memory disorders were also correlated to APOE -ɛ4 allele ( P =0.048) and were more frequent among DLB and PSP carriers. Depression was associated to APOE- ε4 ( P =0.042), more markedly in APOE- ε4-CBS and MSA carriers. Conclusions: Our findings suggested a role of APOE -ε4 in defining a more altered cognitive phenotype with variable degrees across subgroups in APS patients, especially in DLB carriers. This effect mainly concerned executive, memory and orientation functions as well as hallucinations.