Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study

Hanson, Angela J.; Banks, William A.; Saucedo, Hector Hernandez; Craft, Suzanne

doi:10.1159/000444079

Cited by 14 publications

(21 citation statements)

References 40 publications

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“…For example, risk of AD was reported as increased by either being overweight or having type 2 diabetes specifically in APOE4 noncarriers (55). Consistent with our rodent data, Hanson et al (56) found that although women APOE4 carriers under normal conditions had poorer glucose tolerance than women APOE4 noncarriers, a significant relationship between glucose tolerance and plasma Ab was observed only in APOE4 noncarriers. Similarly, another report showed that fasting glucose was positively correlated with cerebral Ab burden only in APOE4 noncarriers (57).…”

Section: Discussionsupporting

confidence: 89%

“…Although obesity and associated metabolic impairments are established risk factors for the development of AD (16), the extent to which APOE genotype impacts this relationship continues to be determined. There are reports that obesity increases AD risk specifically in APOE4 carriers (51,52), however most studies find that the relationship between metabolic impairments and AD risk is strongest in APOE4 noncarriers (28,(53)(54)(55)(56)(57). For example, risk of AD was reported as increased by either being overweight or having type 2 diabetes specifically in APOE4 noncarriers (55).…”

Section: Discussionmentioning

confidence: 99%

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APOEgenotype affects metabolic and Alzheimer‐related outcomes induced by Western diet in female EFAD mice

Christensen

Pike

2018

FASEB j.

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Development of Alzheimer's disease (AD) is regulated by interactive effects of genetic and environmental risk factors. The most significant genetic risk factor for AD is the ε4 allele of apolipoprotein E (APOE4), which has been shown to exert greater AD risk in women. An important modifiable AD risk factor is obesity and its associated metabolic dysfunctions. Whether APOE genotype might interact with obesity in females to regulate AD pathogenesis is unclear. To investigate this issue, we studied the effects of Western diet (WD) on female EFAD mice, a transgenic mouse model of AD that includes human APOE alleles ε3 (E3FAD) and ε4 (E4FAD). EFAD mice were fed either control (10% fat, 7% sugar) or WD (45% fat, 17% sugar), and both metabolic and neuropathologic outcomes were determined. Although E4FAD mice generally exhibited poorer metabolic status at baseline, E3FAD mice showed greater diet‐induced metabolic impairments. Similarly, E4FAD mice exhibited higher levels of AD‐related pathology overall, but only E3FAD showed significant increases on select measures of β‐amyloid pathology after exposure to WD. These data demonstrate a gene–environment interaction between APOE and obesogenic diets in females. Understanding how AD‐promoting effects of obesity are modulated by genetic factors will foster the identification of at‐risk populations and development of preventive interventions.—Christensen, A., Pike, C. J. APOE genotype affects metabolic and Alzheimer‐related outcomes induced by Western diet in female EFAD mice. FASEB J. 33, 4054–4066 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

APOEgenotype affects metabolic and Alzheimer‐related outcomes induced by Western diet in female EFAD mice

Christensen

Pike

2018

FASEB j.

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“…Our finding of increased fasting insulin in both AD subjects and APOE4 non-carriers is partially consistent with recent work, which showed higher fasting insulin in cognitively impaired subjects but no effect of APOE4 status [37]. Differences in assay type, cohort age, and diagnostic characterization of subjects could contribute to these differences.…”

Section: Discussionsupporting

confidence: 92%

Effect of APOE ε4 Genotype on Metabolic Biomarkers in Aging and Alzheimer’s Disease

Morris

Vidoni

et al. 2017

JAD

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Alzheimer's disease (AD) may have heterogeneous pathophysiological underpinnings, with risk factors including apolipoprotein ε4 (APOE4) genotype and insulin resistance. We hypothesized that distinct phenotypes exist within AD. We examined APOE4 and metabolic biomarkers in 338 subjects (n=213 nondemented (ND), n=125 AD). We further characterized steady state free fatty acid (FFA) levels in a subset of 45 participants who had also participated in a hyperinsulinemic-euglycemic clamp. Insulin resistance (HOMA-IR) was elevated in AD vs ND (p=0.04) and in APOE4 noncarriers vs.carriers (p<0.01). This was driven by increased fasting insulin in AD vs. ND (p<0.01) and in APOE4 non-carriers vs carriers (p=0.01). Fasting glucose was not different. In subjects who underwent a clamp, there was a group x genotype interaction on FFA levels during hyperinsulinemia (p=0.03). APOE4 non-carriers with AD had higher FFA levels, while APOE4 carriers with AD exhibited lower FFA levels. Metabolic dysfunction is overrepresented in individuals with AD dementia who do not carry the APOE4 allele. This suggests that important subsets of AD phenotypes may exist that diverge metabolically.

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“…We have previously shown that E4+ individuals demonstrate different metabolic and cognitive responses to macronutrients including high fat and high glucose meals, but this may be the first study to explore the relationship between APOE genotype and PPH in older adults (19, 20). We found that E4+ participants experienced a more substantial decrease in SBP and higher incidence of PPH following both meals.…”

Section: Discussionmentioning

confidence: 96%

“…We and others have shown that E4 status influences the connection between dietary risk factors and AD. For example, E4+ individuals respond differently to high fat feeding and an oral glucose drink compared to their E4− counterparts, suggesting that APOE genotype influences the relationship between diet and cognitive aging (19, 20). …”

Section: Introductionmentioning

confidence: 99%

APOE Genotype Influences Postprandial Blood Pressure After High fat Feeding in Older Adults

Stewart

Subramanian

Neal

et al. 2019

The Journal of nutrition, health and aging

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Objective: Postprandial hypotension (PPH) is a common phenomenon among older adults. The degree to which individuals experience PPH is related to cerebrovascular risk factors and the presence of neurodegenerative diseases such as Alzheimer’s disease (AD). Carrier status of the E4 allele of the apolipoprotein E (APOE) gene is a risk factor for AD and influences a variety of responses to metabolic and dietary interventions. However, it is unknown whether APOE genotype influences the risk of PPH and whether type of meal can mediate that response. Design: Acute meal study with a crossover design. Participants: 32 cognitively healthy older adults with (n=18) and without (n=14) E4+ carrier status. Intervention: As a part of an ongoing meal study we examined the postprandial blood pressure response after ingestion of a high carbohydrate (HCM) and high fat meal (HFM). Measurements: Blood pressure measurements were taken at 7 time points and change scores, area under the curve (AUC) scores were calculated. Data were analyzed by repeated measures ANOVA as well as Pearson correlation. Results: Both meals produced a sustained drop in systolic (SBP) and diastolic (DBP) blood pressure, with 37.5% of participants meeting criteria for PPH. Participants carrying the E4+ risk gene experienced a larger decrease in SBP than E4− participants, and this was significantly different after the HFM (E4+ AUC = −30.8 ± 7.6, E4− AUC = −0.2 ± 8.7, p=0.015). Increasing age was associated with a larger drop in postprandial blood pressure but only for the E4+ group after the HFM (p=0.002). Conclusions: These data suggest that E4+ individuals experience a greater postprandial blood pressure response particularly following high fat feeding, and this effect becomes more pronounced with age. The prevalence of PPH may play a role in the development of AD and may be mediated by diet.

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Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study

Cited by 14 publications

References 40 publications

APOEgenotype affects metabolic and Alzheimer‐related outcomes induced by Western diet in female EFAD mice

APOEgenotype affects metabolic and Alzheimer‐related outcomes induced by Western diet in female EFAD mice

Effect of APOE ε4 Genotype on Metabolic Biomarkers in Aging and Alzheimer’s Disease

APOE Genotype Influences Postprandial Blood Pressure After High fat Feeding in Older Adults

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