Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype.

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)-epsilon 4 allele. Insulin has also been implicated in processing of beta-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 epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an epsilon 4 allele (p < 0.03) or than did normal adults without an epsilon 4 allele (p < 0.02). AD subjects without an epsilon 4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-epsilon 4 group did not. Insulin reduced APP levels for AD patients without an ApoE epsilon 4 allele, but raised APP for AD patients with an ApoE epsilon H4 allele These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.

journal_name

Ann N Y Acad Sci

authors

Craft S,Asthana S,Schellenberg G,Baker L,Cherrier M,Boyt AA,Martins RN,Raskind M,Peskind E,Plymate S

doi

10.1111/j.1749-6632.2000.tb06371.x

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

222-8

eissn

0077-8923

issn

1749-6632

journal_volume

903

pub_type

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