Insulin Effects on Glucose Metabolism, Memory, and Plasma Amyloid Precursor Protein in Alzheimer's Disease Differ According to Apolipoprotein-E Genotype

Authors

  • SUZANNE CRAFT,

    Corresponding author
    1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Departments of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • SANJAY ASTHANA,

    1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • GERARD SCHELLENBERG,

    1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98108, USA
    3. Department of Neurology, University of Washington School of Medicine, Seattle, Washington 98108, USA
    4. Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • LAURA BAKER,

    1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Departments of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • MONIQUE CHERRIER,

    1. Departments of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • ADAM A. BOYT,

    1. Sir James McCusker Alzheimer's Disease Research Unit, Department of Surgery, The University of Western Australia, Perth, Australia
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  • RALPH N. MARTINS,

    1. Sir James McCusker Alzheimer's Disease Research Unit, Department of Surgery, The University of Western Australia, Perth, Australia
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  • MURRAY RASKIND,

    1. Mental Health Services, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Departments of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • ELAINE PESKIND,

    1. Mental Health Services, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Departments of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98108, USA
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  • STEPHEN PLYMATE

    1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    2. Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98108, USA
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Address for correspondence: Suzanne Craft, GRECC 182B, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, Washington 98108. Tel.: 206–764–2308; fax: 206–764–2569. e-mail: scraft@u.washington.edu

Abstract

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)-ɛ4 allele. Insulin has also been implicated in processing of β-amyloid and amyloid precursor protein (APP). We examined the effects of intravenous insulin administration while maintaining euglycemia on insulin-mediated glucose disposal, memory, and plasma APP in patients with AD and normal adults of varying ApoE genotypes. AD subjects without an ɛ4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an ɛ4 allele (p < 0.03) or than did normal adults without an ɛ4 allele (p < 0.02). AD subjects without an ɛ4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-ɛ4 group did not. Insulin reduced APP levels for AD patients without an ApoE ɛ4 allele, but raised APP for AD patients with an ApoE ɛH4 allele These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.

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