The finding comes from the Brown University laboratory of Suzanne M. de la Monte, MD, MPH. Last year, de la Monte proposed that Alzheimer's disease is really "type 3 diabetes" -- that is, a kind of brain diabetes.
De la Monte's suggestion is based on studies in which a poison is used to kill off insulin-producing cells in the brains of baby rats. These rats develop dementia and brain degeneration similar to that seen in Alzheimer's disease.
Supporting this theory is an earlier study of the brain autopsies of Alzheimer's patients, which showed that brain cells sensitive to insulin die off. Moreover, de la Monte and colleagues find, reduced insulin signaling in the brain happens early in the course of Alzheimer's disease -- and gets worse as dementia progresses.
Now de la Monte and colleagues find that an insulin-sensitizing drug protects the brains of rats and keeps them from developing Alzheimer's-like disease.
"This is great news for patients since you treat early stages of disease," de la Monte, said in a news release. "The trigger for dementia is the loss of insulin and insulin-growth-factor-producing cells. The cells that need those growth factors subsequently die. This study shows you can block the second phase, which is responsible for dementia."
The Next Glitazone?
The drug de la Monte and colleagues found so useful for rats is very similar to two drugs currently used to treat diabetes: Actos and Avandia. Known as "TZDs" or "glitazones," the drugs make the body's cells more sensitive to insulin.
They do this by stimulating a cellular molecule called peroxisome-proliferator activated receptor or PPAR. There are several kinds of PPAR. Actos and Avandia stimulate the kind called PPAR-gamma. New "glitazar" drugs now in development will stimulate PPAR-alpha as well as PPAR-gamma.
However, de la Monte and colleagues find that the best anti-Alzheimer's effect -- in rats -- comes from a drug that stimulates a kind of PPAR called PPAR-delta.
The good news is that if this treatment does turn out to work in people, brain injections probably won't be needed. In the rat studies, the drug was able to travel through the blood into the brain.
"Everybody wants something for cognitive impairment, and that was the most improved with the PPAR-delta [stimulator]," de la Monte said.
The study, funded by grants from the National Institutes of Health, appears in the September issue of the Journal of Alzheimer's Disease.