Salk study finds diabetes raises levels of proteins linked to Alzheimer's features
Growing evidence suggests that there may be a link between type 1 diabetes and Alzheimer's disease, but the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. Now, in a study published in Aging Cell, Salk researchers show, for the first time, that diabetes enhances the development of aging features that may underlie early pathological events in Alzheimer's.
The Salk team found increases in two hallmarks of Alzheimer's— accumulations of amyloid beta (Abeta) and tau protein—in the brains of diabetic mice, especially in cells surrounding blood vessels. Abeta, the misfolded peptide that is thought in part to cause Alzheimer's disease, aggregated inside astrocytes, star-shaped brain cells that, upon interaction with Abeta, release inflammatory molecules that can destroy neurons. Previously, this had not been shown in mouse models of type 1 diabetes.
"Our study supports and extends the links between diabetes, aging and Alzheimer's," says author Pamela Maher, a senior staff scientist in Salk's Laboratory of Cellular Neurobiology. "We show that type 1 diabetes increases vascular-associated amyloid beta buildup in the brain and causes accelerated brain aging."
To examine the contributions of diabetes to Alzheimer's-related pathology in the aged brain, the Salk researchers induced type 1 diabetes in two sets of mice. One set, known as SAMP8 mice, undergo accelerated aging and develop early deterioration in learning and memory, as well as a number of brain alterations similar to those found in Alzheimer's. The other set, SAMR1 mice, which in this study came from the same gene pool as the SAMP8 mice, age normally.
Using these mice, Maher and her colleagues addressed how type 1 diabetes interacts with age to contribute to Alzheimer's-related pathology. They showed that diabetes elicits a wide range of pathological changes in the brains of both strains of mice, which are exacerbated by premature aging.
The Salk study is the first to show that these modifications are similar to those seen in old nondiabetic SAMP8 mice and to identify unique pathological changes, such as increases in markers for inflammation, in aged, diabetic SAMP8 mice. Unlike most mouse studies of Alzheimer's, Maher's mice were not engineered to produce high levels of human Abeta or tau, so all of their observations came from naturally occurring Abeta and tau.
The findings suggest that the neurovascular system may be a good candidate for new therapeutic targets to treat Alzheimer's in the early stages of the disease.