Insulin Metabolism in Alzheimer’s Disease Differs According to Apolipoprotein E Genotype and Gender

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)-Ε4 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. Participants were 32 patients with AD (9 without an Ε4 allele, 23 with an Ε4 allele) and 25 healthy age-matched adults (16 without an Ε4 allele, 9 with an Ε4 allele). AD subjects without an Ε4 allele had significantly lower insulin-mediated glucose disposal rates than AD patients with an Ε4 allele (p < 0.03), or than normal adults without an Ε4 allele (p < 0.02). Female AD subjects showed lower insulin-mediated glucose disposal rates than did male AD subjects (p < 0.02). No significant interaction was observed between APOE group and gender, suggesting that these effects are independent. AD subjects without an Ε4 allele also showed significant memory facilitation in the hyperinsulinemic condition (p < 0.04), whereas the AD-Ε4 group did not. Also in the hyperinsulinemic condition, AD patients without an Ε4 allele had lower insulin levels than patients with an Ε4 allele (p < 0.02), and women with AD had lower insulin levels than did men with AD despite similar insulin infusion rates and body mass (p < 0.004). No gender or genotype effects were observed in either condition for normal subjects. These results provide in vivo evidence of differences in insulin-mediated energy metabolism between Ε4 and non-Ε4 AD, and suggest that defective insulin action may be of particular pathophysiologic significance for patients without an Ε-4 allele.

Insulin Levels are Decreased in the Cerebrospinal Fluid of Women with Prodomal Alzheimer's Disease

“…Our results were significant even after controlling for age and gender. These findings are in agreement with previous studies reporting lower CSF-insulin in more advanced AD [13,27]. Two other studies found either increased levels [14] or no changes [15].…”

“…Previous reports have shown that non-homozygotes for the ε4 allele had higher plasma insulin than ε4 carriers [13,27]. In the present study, no significant differences in CSF-insulin were found between ApoE ε4 carriers and non-carriers, although it is possible that the number of samples in our study would limit the detection of differences in ApoE subgroups.…”

“…There is little data on gender differences in insulin levels/function in AD, and no reports regarding AD progression. Female AD subjects have been shown to have lower plasma insulin levels compared to males [27]. An interaction between some gonadal hormonal system (that could be affected in post-menopausal women with AD) and brain insulin synthesis or degradation, could also be hypothesized.…”

Does gender play a role in Alzheimer therapy?

“…Women with Alzheimer's disease exhibit greater heterogeneity in regional cerebral blood flow than men, asymmetry in cerebral blood flow occurs more often in women [11]. Insulin metabolism is differently affected by Alzheimer's disease in females and males [12]. There are also gender differences in genetic 'There are gender differences in genetic instability and the effect of an apolipoprotein E4 allele on the risk of Alzheimer's disease seems more pronounced in females.…”

Multi-detector CT angiography in intracranial dural AV fistula at the foramen magnum

“…ApoE4 per se increases the risk for coronary artery disease 30 and for AD. 31 In addition, ApoE has been shown to interact with several cardiovascular risk factors, such as hypertension, 32 cholesterol, 33 insulin resistance, 34 and transient ischemic attacks, 35 to increase the incidence of AD and to accelerate its course. In view of these direct and indirect associations, ApoE might be serving as a common intermediary of both coronary artery disease and AD neuropathology.…”