Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer’s disease (AD) by geographic region and country. Methods: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Results: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5–51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4–10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9–66.7), e4/4 prevalence: 14.1% (95% CI: 12.2–16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. Conclusions: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.

Clinical presentation of chronic traumatic encephalopathy

“…Although interpretation and generalization of these results is difficult because of the small sample, the proportion of e4 homozygosity is in contrast to population norms in which e4 homozygosity only occurs in 1% to 3% of the general population, 17 and more consistent with the 10% of patients with AD who are e4 homozygous. 18 The APOE e4 variant is the largest known genetic risk factor for sporadic AD. 18 It has been associated with b-amyloid, but not tau, deposition in cognitively normal aging.…”

“…18 The APOE e4 variant is the largest known genetic risk factor for sporadic AD. 18 It has been associated with b-amyloid, but not tau, deposition in cognitively normal aging.…”

Apolipoprotein E region molecular signatures of Alzheimer's disease

“…Heterogeneity in the strongest genetic risk factor for ADs, the APOE e4 allele, is evidenced by differences between geographic gradients in the frequency of the e4 allele among AD‐affected and general populations. Indeed, for Caucasians, the AD gradient ranges from 40.5% in Southern Europe to 61.3% in Northern Europe (Ward et al., 2012), whereas in the general population, the gradient is much wider, ranging from 10% to 15% in Southern Europe to 40%–50% in Northern Europe (Gerdes, 2003). This heterogeneity suggests that individuals carrying the e4 allele might not develop an AD.…”

The Correlation between Genotype and Phenotype of Alzheimer's Disease

“…The fact that ApoE4 does not bind to tau protein in vitro suggested that this interaction between ApoE3 and tau serves as a protection against tau phosphorylation and consequent neurofibrillary tangle formation [58]. In a recent metaanalysis, Ward et al [60] studied the prevalence of ApoE4 genotype among patients with AD in different regions. The pooled estimates for APOE ε4 carrier prevalence is 48.7% and ε4/4 prevalence 9.6%.…”