Confirmed Synergy Between the ɛ4 Allele of Apolipoprotein E and the Variant K of Butyrylcholinesterase as a Risk Factor for Alzheimer's Disease: A Systematic Review and Meta-Analysis

Renan C Ratis; Maria I Dacoregio; Daiane P Simão-Silva; Rogério P Mateus; Luciana P B Machado; Juliana S Bonini; Weber Claudio Francisco Nunes da Silva

doi:10.3233/ADR-220084

Confirmed Synergy Between the ɛ4 Allele of Apolipoprotein E and the Variant K of Butyrylcholinesterase as a Risk Factor for Alzheimer's Disease: A Systematic Review and Meta-Analysis

J Alzheimers Dis Rep. 2023 Jun 19;7(1):613-625. doi: 10.3233/ADR-220084. eCollection 2023.

Authors

Renan C Ratis¹, Maria I Dacoregio², Daiane P Simão-Silva³, Rogério P Mateus⁴, Luciana P B Machado⁴, Juliana S Bonini¹, Weber Claudio Francisco Nunes da Silva⁵

Affiliations

¹ Laboratory of Neurosciences and Behavior, Department of Pharmacy, State University of the Midwest, Paraná, Brazil.
² Faculty of Medicine, State University of the Midwest, Paraná, Brazil.
³ Post-Graduate Program in Intellectual Property and Technology Transfer for Innovation, State University of the Midwest, Paraná, Brazil.
⁴ Evolutionary Biology Laboratory, Department of Biology, State University of the Midwest, Paraná, Brazil.
⁵ Laboratory of Neuropsychopharmacology, Department of Pharmacy, State University of the Midwest, Paraná, Brazil.

Abstract

Background: Alzheimer's disease (AD) has several risk factors. APOE4 is the main one, and it has been suggested that there may be a synergy between it and BCHE-K as a risk factor.

Objective: To investigate the association between APOE4 and BCHE-K as a risk factor for AD.

Methods: We searched PubMed, Web of Science, Embase, and Scopus on August 8, 2021 for studies that analyzed the association of APOE4 and BCHE-K with AD. The random effect model was performed in meta-analysis according to age group. A chi-square was performed with the meta-analysis data to verify if the effect found is not associated only with the E4 allele.

Results: Twenty-one studies with 6,853 subjects (3,528 AD and 3,325 Controls) were included in the meta-analysis. The quality of the evidence is moderate. There is a positive E4-K association for subjects with AD as shown by the odds ratio of 3.43. The chi-square meta test, which measures the probability that the E4-K association is due to chance, has an odds ratio of 6.155, indicating that the E4-K association is not a random event. The odds ratio of an E4-K association in subjects with AD increases to OR 4.46 for the 65- to 75-year-old group and OR 4.15 for subjects older than 75 years. The probability that the E4-K association is due to chance is ruled out by chi-square meta test values of OR 8.638 and OR 9.558.

Conclusion: The synergy between APOE4 and BCHE-K is a risk factor for late-onset AD.

Keywords: APOE; Alzheimer’s disease; BaβAC; cholinesterase; dementia; genetics; odds ratio.

Publication types

Systematic Review