S. Craft et al., Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender, NEUROENDOCR, 70(2), 1999, pp. 146-152
Higher fasting plasma insulin levels and reduced CSF-to-plasma insulin rati
os, suggestive of insulin resistance, have been observed in patients with A
lzheimer's disease (AD) who do not possess an apolipoprotein E (APOE)epsilo
n E4 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. Participan
ts were 32 patients with AD (9 without an epsilon 4 allele, 23 with an epsi
lon 4 allele) and 25 healthy age-matched adults (16 without an epsilon 4 al
lele, 9 with an epsilon 4 allele). AD subjects without an epsilon 4 allele
had significantly lower insulin-mediated glucose disposal rates than AD pat
ients with an epsilon 4 allele (p < 0.03), or than normal adults without an
epsilon 4 allele (p < 0.02). Female AD subjects showed lower insulin-media
ted glucose disposal rates than did male AD subjects (p < 0.02). No signifi
cant interaction was observed between APOE group and gender, suggesting tha
t these effects are independent. AD subjects without an epsilon 4 allele al
so showed significant memory facilitation in the hyperinsulinemic condition
(p < 0.04), whereas the AD-epsilon 4 group did not. Also in the hyperinsul
inemic condition, AD patients without an epsilon 4 allele had lower insulin
levels than patients with an epsilon 4 allele (p < 0.02), and women with A
D had lower insulin levels than did men with AD despite similar insulin inf
usion rates and body mass (p < 0.004). No gender or genotype effects were o
bserved in either condition for normal subjects. These results provide in v
ivo evidence of differences in insulin-mediated energy metabolism between e
psilon 4 and non-epsilon 4 AD, and suggest that defective insulin action ma
y be of particular pathophysiologic significance for patients without an ep
silon-4 allele.