Behavioural effects of the ACE insertion/deletion polymorphism in Alzheimer's disease depend upon stratification according to APOE-ϵ4 carrier status

• Published in: Cognitive neuropsychiatry Vol. 26; no. 4; pp. 293 - 305
• Main Authors: Oliveira, Fabricio Ferreira de, de Almeida, Sandro Soares, Smith, Marilia Cardoso, Bertolucci, Paulo Henrique Ferreira
• Format: Journal Article
• Language: English
• Published: England Routledge 01-07-2021; Taylor & Francis Ltd
• Subjects: Age; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - genetics; Alzheimer's disease; ApoE; Apolipoproteins E - genetics; behavioural symptoms; Dementia; Female; genetics; Genotype; Humans; Male; Polymerase chain reaction; Polymorphism; Polymorphism, Genetic; renin-angiotensin system; behavioural symptoms; ApoE; genetics; Alzheimer disease; renin-angiotensin system
• ISSN: 1354-6805; 1464-0619
• DOI: 10.1080/13546805.2021.1931085

Introduction: The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of APOE and ACE with age at AD onset and with neuropsychiatric symptoms according to each dementia stage.
Methods: Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 (APOE haplotypes, Real-Time Polymerase Chain Reactions), and the ACE insertion/deletion polymorphism (Polymerase Chain Reactions). Combined genetic variants of APOE and ACE were associated with age at dementia onset, and with neuropsychiatric symptoms in each dementia stage (adjusted for sex and age at dementia onset).
Results: Over two-thirds of the 238 patients were women, whereas the mean age at dementia onset was 73.82 ± 6.2 years-old. APOE-ϵ4/ϵ4 carriers had earlier dementia onset (p<.001). The ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p=.37) but was not associated with age at dementia onset, regardless of APOE-ϵ4 carrier status. The only results that survived corrections for false discovery rates were higher scores of dysphoria for APOE-ϵ4 carriers (n=122) who also carried ACE deletion/deletion (p=.031). No results survived corrections for false discovery rates for APOE-ϵ4 non-carriers (n=116).
Conclusions: Though only the APOE-ϵ4/ϵ4 haplotype affected AD onset, effects of the ACE insertion/deletion polymorphism over behavioural features might differ according to APOE-ϵ4 carrier status in genetic associations.