Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

Neu, Scott; Pa, Judy; Kukull, Walter A.; Beekly, Duane; Kuzma, Amanda B.; Gangadharan, Prabhakaran; Wang, Li San; Romero, Klaus; Arnerić, Stephen P.; Redolfi, Alberto; Orlandi, Daniele; Frisoni, Giovanni B.; Au, Rhoda; Devine, Sherral; Auerbach, Sanford; Espinosa, Ana; Boada, Merçé; Ruiz, Agustín; Johnson, Sterling C.; Koscik, Rebecca L.; Wang, Jiun‐Jie; Hsu, Wen‐Chuin; Chen, Yao Liang; Toga, Arthur W.

doi:10.1001/jamaneurol.2017.2188

Cited by 470 publications

(406 citation statements)

References 77 publications

(132 reference statements)

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“…We found that the interaction between gender and APOE did not have a significant effect on the odds for AD neither for controls (p = 0.984) nor for the MCI patients (p = 0.799). These findings are in line with the aforementioned meta-analysis [50].…”

Section: Discussionsupporting

confidence: 91%

“…However, many other factors should also be considered to explain the sex differences; for a review, see [49]. A recent meta-analysis suggests similar odds of developing MCI and AD [50]. According to our analysis, the odds of AD for MCI males ε4-homozygotes are 5.933-fold higher than those with the ε3/3 (OR 5.933, 95% CI 1.319-26.688, p = 0.020), while the odds for AD of MCI females ε4-homozygotes are 6.873-fold higher than those with the ε3/3 (OR 6.873, 95% CI 2.758-17.127, p < 0.001).…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

et al. 2018

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Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

et al. 2018

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“…These include predominantly gastric diseases such as Helicobacter pylori infection, atrophic gastritis, gastric surgery [20], or cancer [21] but also include inflammatory bowel disease [22], diabetes mellitus, or thyroid diseases [20]. As the current study encompassed a healthy population, it is unlikely that an underlying significant disease could mediate the association between men and vitamin B12 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort

et al. 2018

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Background: Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. Methods: A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18–65, who were provided with a routine medical evaluation during 2000–2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. Results: In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43–3.56). Conclusions: Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role.

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“…A neuroimaging study using FDG-PET showed that women who were ε4 carriers had significantly more brain hypometabolism and cortical thinning compared to non-carriers, while the difference between ε4 carriers and non-carriers in men was much less substantial (90). However, recent evidence suggests that ε4 carrier status may confer the greatest risk for women between the ages of 65-75, and may not confer additional risk compared to men outside of that age bracket (91). Therefore, it is important to consider sex differences when evaluating for AD risk, and additional research may help to elucidate the multi-factorial relationship seen among sex, ε4 carrier status, age, and other factors such as menopause.…”

Section: Other Apoe-related Considerationsmentioning

confidence: 99%

Clinical Application of Apoe in Alzheimer’s Prevention: A Precision Medicine Approach

et al. 2018

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Population-attributable risk models estimate that up to one-third of Alzheimer’s disease (AD) cases may be preventable through risk factor modification. The field of AD prevention has largely focused on addressing these factors through universal risk reduction strategies for the general population. However, targeting these strategies in a clinical precision medicine fashion, including the use of genetic risk factors, allows for potentially greater impact on AD risk reduction. Apolipoprotein E (APOE), and specifically the APOE ε4 variant, is one of the most well-established genetic influencers on late-onset AD risk. In this review, we evaluate the impact of APOE ε4 carrier status on AD prevention interventions, including lifestyle, nutrigenomic, pharmacogenomic, AD comorbidities, and other biological and behavioral considerations. Using a clinical precision medicine strategy that incorporates APOE ε4 carrier status may provide a highly targeted and distinct approach to AD prevention with greater potential for success.

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Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

Cited by 470 publications

References 77 publications

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort

Clinical Application of Apoe in Alzheimer’s Prevention: A Precision Medicine Approach

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