Elsevier

Neuroscience

Volume 95, Issue 3, December 1999, Pages 727-734
Neuroscience

The effect of insulin and glucose on the plasma concentration of Alzheimer's amyloid precursor protein

https://doi.org/10.1016/S0306-4522(99)00458-3Get rights and content

Abstract

The deposition of beta amyloid is a critical event in the pathogenesis of Alzheimer's disease. This peptide is a metabolite of the amyloid precursor protein. Recent research suggests that there is a correlation between plasma insulin and glucose concentrations and memory performance in Alzheimer's disease sufferers. Additionally, in vitro evidence suggests that both insulin and glucose may affect the metabolism of amyloid precursor protein and therefore the production of beta amyloid—however, to our knowledge no in vivo data have yet been published. We investigated the effect of elevated plasma levels of glucose and insulin on the plasma concentration of amyloid precursor protein in non-Alzheimer's disease subjects. As would be expected following ingestion of a glucose drink, blood insulin and glucose levels significantly increased. Interestingly, however, plasma amyloid precursor protein concentration decreased. Whilst no correlation was observed between insulin or glucose levels and plasma amyloid precursor protein concentration, the decrease in plasma amyloid precursor protein concentration was affected by the apolipoprotein E genotype of the subject. Possession of an ϵ4 allele resulted in a reduced decrease in plasma amyloid precursor protein in response to glucose ingestion when compared to non-ϵ4 subjects.

We conclude that glucose ingestion, and the subsequent elevation of plasma levels of glucose and insulin leads to a decrease in plasma amyloid precursor protein concentration. Further studies are required to determine the clinical significance of these physiological changes in plasma amyloid precursor protein and the implications for Alzheimer's disease pathogenesis.

Section snippets

Materials

Acrylamide, piperazine diacrylamide, N′N′N′N′-tetra-methylethylenediamine, ammonium persulphate, sodium dodecyl sulfate, N-tris(hydroxymethyl)methylglycine (tricine) and nitrocellulose membrane (0.2 μm pore size) were purchased from Biorad Laboratories (Hercules, CA). Tris(hydroxymethyl)methylamine (Tris) and polyoxyethylene(20)sorbitan monolaurate (Tween-20) were purchased from BDH (Poole, U.K.). Heparin-sepharose beads were purchased from Pharmacia Biotech (Little Chalfont, U.K.). The

Results

Blood was collected from 14 control subjects following a 10 h fast. The mean age of the group was 31 years (S.E.M.=±2.80). ApoE genotype analysis revealed 12 subjects with an ApoE genotype of ϵ3/ϵ2, 12 with ApoE ϵ3/ϵ3 and two with ApoE ϵ3/ϵ4 genotype.

Analysis of blood insulin concentrations revealed an increase, from a mean fasting concentration of 7.40 mU/l (S.E.M.=±1.29), to a mean maximal value of 40.2 mU/l (S.E.M.=±29.5), 1 h following glucose ingestion, before dropping back to near-fasting

Discussion

Previously published reports have described an association between diabetes and AD and more specifically a link between insulin, glucose and AD. Insulin and glucose may both be involved in the metabolism and action of APP and Aß. In this paper we describe the effects of glucose ingestion on the concentration (and therefore uptake/secretion) of APP in non-diabetic subjects. We report that the resulting increase in blood insulin concentration, following an increase in glucose concentration, is

Acknowledgements

Special thanks go to all the volunteers who participated in this study. The excellent assistance of Athena Paton, Georgia Martins and Peter Lewis is most appreciated for collection and processing of blood samples. This work is supported by grants to R.N.M. from The McCusker Alzheimer's Disease Research Foundation, the Department of Veteran Affairs and the N.H. and M.R.C.

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