👤 Alberto Montesanto

The apolipoprotein E (APOE) gene represents the strongest genetic determinant of sporadic Alzheimer's disease (AD), yet its interaction with sex-specific endocrine factors remains poorly understood. Lifetime estrogen exposure, estimated through reproductive lifespan, may modulate neurodegenerative risk, but findings are inconsistent. Previous studies have examined reproductive factors and APOE interactions in relation to cognitive outcomes, but dose-dependent effects across all APOE alleles (ε2, ε3, ε4) in clinically diagnosed AD patients remain underexplored. This study investigates the joint effects of reproductive lifespan, age at natural menopause (ANM), and APOE genotype on AD risk in females. A total of 396 female participants (103 with AD, 293 cognitively healthy controls) were retrospectively analyzed. Demographic, clinical, and reproductive data were extracted from medical records. APOE genotyping was performed by sequencing rs429358 and rs7412 polymorphisms. Logistic regression models tested associations between ANM, reproductive lifespan, and AD diagnosis, adjusting for education, body mass index (BMI), smoking, diabetes, hypertension, and number of children. Moderation analyses assessed the interaction between reproductive variables and APOE ε2, ε3, and ε4 alleles, and were followed by simple slope analyses to clarify the direction of significant effects. AD females exhibited later ANM (50.3 ± 4.4 vs. 48.3 ± 6.2 years; This work provides novel evidence that extended ovarian function is associated with increased AD vulnerability in females, particularly among APOE ε4 carriers. These findings highlight a dose-dependent, genotype-specific interaction between reproductive aging and neurodegeneration, suggesting APOE as a molecular bridge linking estrogenic exposure and AD risk. Show less

Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the Show less

Several genetic variants playing a key role in cholesterol levels, blood pressure, and vascular dysfunction influence the risk of Alzheimer's disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried out on large numbers of samples in different populations have not provided clear results to date, because a trans-ethnic shift of risk genotypes in different populations is often observed. To determine genotypes allele frequencies of the polymorphisms most frequently identified to be correlated with cardio-cerebrovascular disease and AD in a Southern Italy population and to investigate their possible association with dementia. The genotype and allele frequencies of 13 cardio-cerebrovascular risk polymorphisms were assessed and their possible association with dementia was investigated in a case-control study, including 221 consecutive unrelated subjects diagnosed with dementia (120 subjects affected by AD, 55 by frontotemporal dementia, and 33 by vascular dementia) and 218 matched controls of Calabrian origin. Carriers of at least one APOEɛ4 allele resulted to be at higher risk of AD [OR(95% CI) = 2.721(1.477-5.011)] and VaD [OR(95% CI) = 6.205(2.356-16.342)] compared to non-carriers. Individuals with the IV genotype of the CETP polymorphism were more likely to have AD [OR(95% CI) = 2.427(1.364-4.319)] and VaD [OR(95% CI) = 3.649(1.455-9.152)] compared to subjects with the II-VV genotypes. CETP I405V polymorphism is likely a risk factor for AD and VaD in our cohort, independent of APOEɛ4 status. Unmodifiable genetic risk factors should be taken into account to promote a healthy lifestyle to prevent dementia. Show less