Insulin resistance occurs in the brains of people with Alzheimer's

The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer's disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways. There was less insulin activation in Alzheimer's cases than in tissue from people who had died without brain disease. Other proteins linked to insulin action in the brain were abnormal in Alzheimer's disease samples. These abnormalities were highly correlated with episodic memory and other cognitive disabilities in the Alzheimer's disease patients.

In tissue from people with Alzheimer's disease and mild cognitive impairment (MCI), researchers found that changes to a protein called insulin receptor substrate-1 (IRS-1 pS636/639 and pS616) in brain cells were linked to the severity of memory impairments regardless of age, sex, diabetes history, or apolipoprotein E (APOE) gene status. Levels of IRS-1 were also significantly associated with, but not likely to affect, the presence of amyloid beta plaques and neurofibrillary tangles, the signature markers of Alzheimer's disease. This suggests that insulin resistance contributes to cognitive decline independent of the classical pathology of Alzheimer's disease.

Researchers noted that three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer's disease and MCI. "Clinical trials would need to be conducted to determine the impact the drugs have on Alzheimer's disease and MCI in non-diabetic patients," said Dr. Arnold.

Source: University of Pennsylvania School of Medicine