Alzheimer’s May be Insulin-Dependent Disease
|
|
Insulin and associated signaling molecules begin to disappear from the brain during early Alzheimer’s, suggesting the possibility of therapy to boost levels of insulin in the brain, researchers here reported. They call Alzheimer’s “type 3 diabetes.”
Mean levels of insulin, the signaling molecule insulin-like growth factor I (IGF-I), and its receptor decline significantly in the brain during the early stages of Alzheimer’s, compared with normal controls, and decrease by 80% or more in late-stage disease, according to Suzanne M. de la Monte, M.D., and colleagues at Brown Medical School here.
Levels of insulin-like growth factor II (IGF-II ) and its receptor also decline during the early stages of Alzheimer’s, but less dramatically, falling to about 50% of normal in late-stage disease, Dr. de la Monte and colleagues reported in the November issue of the Journal of Alzheimer’s Disease.
The researchers analyzed postmortem brain tissue from 45 patients with a diagnosis of either normal aging or Alzheimer’s. Samples from patients with Alzheimer’s were histologically graded according to disease severity.
The researchers also found that levels of the enzyme choline acetyltransferase (ChAT), which is responsible for making acetylcholine, were 65% to 70% lower in samples from late-stage disease than normal controls. Acetylcholine deficiency has been linked to dementia and has long been recognized as an early abnormality in Alzheimer’s.
Further tests on cultured human neuronal cells revealed that insulin and IGF-I stimulate the expression of ChAT, leading the researchers to speculate that acetylcholine deficiency may be caused by declining levels of insulin and IGF-I.
“Altogether, the results suggest that impairments in insulin, IGF-I, and IGF-II stimulated signaling and associated reductions in energy metabolism (ATP) and ChAT expression represent major abnormalities that develop early in the course of Alzheimer’s disease and progress with severity of neurodegeneration,” the researchers said.
Furthermore, the findings “support our hypothesis that Alzheimer’s disease represents a neuroendocrine disease that shares features with Types 1 and 2 diabetes mellitus, and which we refer to as ‘type 3 diabetes,’” they concluded.
“From the standpoint of therapeutic intervention, treatment with ligands that specifically enhance insulin/IGF-I/IGF-II signaling mechanisms in the brain may help to improve viability and function of neuronal cells at risk for Alzheimer’s disease-type neurodegeneration,” the researchers suggested.
Implanted stem cells that deliver a continuous source of insulin or associated signaling molecules might one day become an effective long-term therapy for Alzheimer’s, they said.
Source: Journal of Alzheimer’s Disease
Print Version
Tell-a-Friend comments powered by Disqus
