Objective: This meta-analysis with a systematic review was undertaken to assess the association between
APOE allelic genotypes and the risk of Alzheimer’s disease (AD) in the Italian population.
Methods: The Web of Science, PubMed, and Scopus databases were searched until 15 November 2023. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using fixed and random effect models, depending on the I
2 statistic value. The systematic review and meta-analysis were conducted in agreement with the PRISMA guideline and registered with PROSPERO (CRD42023492580).
Results: Our meta-analysis based on 15 studies revealed a higher risk of AD among Italian individuals carrying the
APOE ε4 allele (OR = 3.60, 95% CI [2.90–4.47],
p < 0.0001). The association of AD genotype
APOE ε2ε4 (OR = 1.36, 95% CI [0.76–2.41],
p = 0.29) was not statistically significant, while
APOE ε3ε4 (OR = 3.43, 95% CI [2.95–3.99],
p < 0.0001) has a high risk of AD development; the risk is more notably in the
APOE ε4ε4 genotype (OR = 7.08, 95% CI [4.22–11.86],
p < 0.0001). The
APOE ε2 allele has a protective effect (
APOE ε2 (OR = 0.47, 95% CI [0.29-0-74],
p = 0.0013)), and similar results were achieved by
APOE ε3 (OR = 0.49, 95% CI [0.37–0.65],
p < 0.0001). Subgroup analysis of three areas of Italy (southern, northern, and center) revealed that that
APOE ε4 allele was a risk factor with a higher OR in northern Italy (OR 4.22; 95% CI [3.46–5.16],
p < 0.0001) compared to southern and center Italy (OR 3.02; 95% CI [2.28–4.01],
p < 0.0001 and OR 3.97; 95% CI [1.37–11.56],
p < 0.0001, respectively). As well,
APOE ε4ε4 genotype carriers had a significantly higher OR in northern Italy (OR 9.69; 95% CI [4.94–18.99],
p < 0.0001) compared to in southern and center Italy (OR 4.38; 95% CI [1.54–12.47],
p < 0.0001 and OR 3.59; 95% CI [0.87–14.86],
p < 0.0001, respectively).
Conclusions: This systematic review with a meta-analysis of the Italian population on
APOE alleles, genotyping, and AD incidence, highlights that individuals harboring
APOE ε4 have a higher risk of developing AD compared to those with other alleles. It also supports the protective effect of the
APOE ε2 allele against the progress of AD. The qualitative analysis on the complex genetic interactions influencing Alzheimer risk emphasizes the need for further research on genetic and environmental factors for effective prevention strategies.
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