APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson’s disease

Abstract

The relationship between APOE polymorphisms and Parkinson’s disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13–3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19–0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

BIN3rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson’s disease

“…Particularly, numerous mutated genes, such as GBA 12,22,24 , LRRK2 [25][26][27] , PRKN 28,29 , PINK1 14,29 , and SNCA 27,30 have been demonstrated to modify the clinical heterogeneity of familial PD patients. In idiopathic PD, a number of genetic variants are found to be associated with the heterogeneity of clinical manifestations [31][32][33][34] . Yoshino et al (2022) identified 13 novel PRKN variants and revealed that patients with different PRKN variants showed heterogenous clinical features dependent on the number of alternate alleles 34 .…”

“…According to previous studies, the motor function of idiopathic PD patients were associated with variants in SNCA 36,37 , BST1 38 , ATP8B2 39 , PARK16 40 , and APOE 41 . Additionally, variants of APOE 31,32 , SNCA 42 , TMEM106B 43 , COMT 44 , MAPT 23,44 , PICALM 45 have been found to be associated with variability of cognitive function in idiopathic PD patients. Nevertheless, the associations between genetic variations and clinical features in sporadic PD remain largely elusive and deserved to be further explored.…”

Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson’s Disease in African and African Admixed Populations

“…There have been only a few published studies exploring PD genetics in the African and African admixed populations, conducted with fewer than thirty samples in all instances 50,51,52,53,54 . In the present study, we have gathered the largest collection of PD patients and controls from African and African admixed ancestry populations to comprehensively assess the genetic architecture of PD on a genome-wide scale.…”

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

“…Published evidence has occasionally suggested that the presence of at least one APOE4 copy is related to earlier PD onset while the presence of APOE3 and/or APOE2 alleles may delay its onset [79][80][81][82][83]. At the same time, the vast majority of published reports failed to reproduce these associations precluding any relationship between APOE and age of PD onset [84][85][86][87][88][89].…”