Cited by 154Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

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Insulin Metabolism in Alzheimer’s Disease Differs According to Apolipoprotein E Genotype and Gender

Craft, Suzanne, Asthana, Sanjay, Schellenberg, Gerard, Cherrier, Monique, Baker, Laura D., Newcomer, John, Plymate, Stephen, Latendresse, Shawn, Petrova, Andreana, Raskind, Murray, Peskind, Elaine, Lofgreen, Cassin, Grimwood, Karla·1999·Neuroendocrinology

DOI 10.1159/000054469

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Abstract

Higher fasting plasma insulin levels and reduced CSF-to-plasma insulin ratios, suggestive of insulin resistance, have been observed in patients with Alzheimer's disease (AD) who do not possess an apolipoprotein E (APOE)-epsilon4 allele. We examined the relationship of APOE and gender to peripheral insulin action and hyperinsulinemic memory facilitation in patients with AD using a sensitive measure of insulin-mediated glucose disposal. Participants were 32 patients with AD (9 without an epsilon4 allele, 23 with an epsilon4 allele) and 25 healthy age-matched adults (16 without an epsilon4 allele, 9 with an epsilon4 allele). AD subjects without an epsilon4 allele had significantly lower insulin-mediated glucose disposal rates than AD patients with an epsilon4 allele (p < 0.03), or than normal adults without an epsilon4 allele (p < 0.02). Female AD subjects showed lower insulin-mediated glucose disposal rates than did male AD subjects (p < 0.02). No significant interaction was observed between APOE group and gender, suggesting that these effects are independent. AD subjects without an epsilon4 allele also showed significant memory facilitation in the hyperinsulinemic condition (p < 0.04), whereas the AD-epsilon4 group did not. Also in the hyperinsulinemic condition, AD patients without an epsilon4 allele had lower insulin levels than patients with an epsilon4 allele (p < 0.02), and women with AD had lower insulin levels than did men with AD despite similar insulin infusion rates and body mass (p < 0.004). No gender or genotype effects were observed in either condition for normal subjects. These results provide in vivo evidence of differences in insulin-mediated energy metabolism between epsilon4 and non-epsilon4 AD, and suggest that defective insulin action may be of particular pathophysiologic significance for patients without an epsilon-4 allele.

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Authors: Craft, S., Asthana, S., Schellenberg, G., Cherrier, M., Baker, L. D., Newcomer, J., Plymate, S., Latendresse, S., Petrova, A., Raskind, M., Peskind, E., Lofgreen, C., & Grimwood, K.
Affiliations: University of Washington (US)
Geriatric Research Education and Clinical Center (US)
Washington University in St. Louis (US)
VA Puget Sound Health Care System (US)
ORCID: Craft, Suzanne
Asthana, Sanjay
Schellenberg, Gerard
Cherrier, Monique
Baker, Laura D.
Newcomer, John
Plymate, Stephen
Latendresse, Shawn
Raskind, Murray
Peskind, Elaine
Venue: Neuroendocrinology
Publisher: S. Karger AG
Published: 1999
Volume: 70
Issue: 2
Pages: 146-152
ISSN: 0028-3835 (ISSN-L)
1423-0194
DOI: 10.1159/000054469
OpenAlex: W1967564647
Cited by: 154
References: 30
Citations by year: 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 5
FWCI: 1.32
Type: journal article
Language: en
Open access: closed
Licence: www.karger.com/Services/SiteLicenses (vor)
www.karger.com/Services/SiteLicenses (tdm)
Locations: Neuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institute on Aging (R01-AG-10880, R01AG010880)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: Alzheimer's disease, apolipoprotein E, APOE ε4, insulin resistance, insulin-stimulated glucose disposal, sex differences, insulin action, energy metabolism, fasting insulin
MeSH terms: Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Blood Glucose, Female, Genotype, Humans, Insulin, Male, Risk Factors, Sex Characteristics, Body Mass Index

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Insulin Metabolism in Alzheimer’s Disease Differs According to Apolipoprotein E Genotype and Gender

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