Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype.
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.
Craft
S
S
Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108, USA. scraft@u.washington.edu
Asthana
S
S
Schellenberg
G
G
Baker
L
L
Cherrier
M
M
Boyt
A A
AA
Martins
R N
RN
Raskind
M
M
Peskind
E
E
Plymate
S
S
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005838:Genotype; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008568:Memory / Q000502:physiology*; D012016:Reference Values
D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin