TY - JOUR
T1 - Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype
AU - Craft, Suzanne
AU - Asthana, Sanjay
AU - Schellenberg, Gerard
AU - Baker, Laura
AU - Cherrier, Monique
AU - Boyt, Adam A.
AU - Martins, Ralph N.
AU - Raskind, Murray
AU - Peskind, Elaine
AU - Plymate, Stephen
PY - 2000
Y1 - 2000
N2 - 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)-ε4 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 ε4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an ε4 allele (p < 0.03) or than did normal adults without an ε4 allele (p < 0.02). AD subjects without an ε4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-ε4 group did not. Insulin reduced APP levels for AD patients without an ApoE ε4 allele, but raised APP for AD patients with an ApoE εH4 allele. These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.
AB - 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)-ε4 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 ε4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an ε4 allele (p < 0.03) or than did normal adults without an ε4 allele (p < 0.02). AD subjects without an ε4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-ε4 group did not. Insulin reduced APP levels for AD patients without an ApoE ε4 allele, but raised APP for AD patients with an ApoE εH4 allele. These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=0034016848&partnerID=8YFLogxK
M3 - Article
C2 - 10818510
AN - SCOPUS:0034016848
SN - 0077-8923
VL - 903
SP - 222
EP - 228
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -