There are two forms of diabetes that most people are familiar with, Type 1 and Type 2. Type 1 is when a person is born with diabetes and has an onset of the disease early in life. Type 2 diabetes usually has an adult onset and is frequently due to diet, weight and other environmental factors.
There could soon be a third type, however. Research into Alzheimer's disease (AD) shows a connection between how the brain processes glucose and the severity of protein plaques in the brain that are the hallmark of AD and other forms of dementia. A study commissioned by the National Institute on Aging and the National Institutes of Health showed that when the brain doesn't break down sugar correctly, the result can be a form of "diabetes of the brain." Disruption in this brain function is directly related to symptoms of AD outwardly and within the brain structure.
Madhav Thambisetty, M.D., Ph.D. was the lead investigator on the work and is also the chief of the Unit of Clinical and Translational Neuroscience in the NIA's Laboratory of Behavioral Neuroscience. The research looked at brain tissue samples from volunteers who agreed to donate their brains to the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is a long-term look at human aging, running over several decades to track psychological, neurological and physical data related to growing older.
The researchers took measurements of glucose levels from cross-sections of brain tissue from different areas. Some of the regions included those known to be involved in AD pathology including the frontal and temporal cortex. Measurements were also taken from the cerebellum which is resistant to the plaques of tau protein found in dementia patients.
Investigators organized the study participants into three groups: Patients who had symptoms of AD during life and beta-amyloid plaques found in post-mortem examinations, those with no signs while they were alive, but evidence of AD in the brain after death, and healthy individuals with no dementia symptoms or pathology.
Glycolysis, the process that the brain uses to break down sugar was analyzed as well. The result showed that individuals that had poor glycolysis and higher levels of glucose in the brain also had more severe symptoms of AD during their life as well as more significant amounts of beta-amyloid plaques and nerve tangles in the brain.
NIA Director Richard J. Hodes, M.D stated, "For some time, researchers have thought about the possible links between how the brain processes glucose and Alzheimer's. Research such as this involves new thinking about how to investigate these connections in the intensifying search for better and more effective ways to treat or prevent Alzheimer's disease."
Many research studies have noted similar characteristics in patients with diabetes and those with Alzheimer's, but the connection was difficult to prove since measuring how the brain uses glucose cannot be done directly. The team on the NIA research looked at ratios of amino acids to glucose to reveal how the brain gets rid of excess sugar. These calculations showed that when glycolysis isn't optimal, dementia can be the result. The team studied the action of a particular protein as well, GLUT3, which transports glucose to neurons and found low levels of this protein were associated with higher levels of AD plaques. Finally, patients who had more elevated blood glucose levels while they were alive also had higher levels of brain glucose when they died. Dr. Thambisetty stated, "These findings point to a novel mechanism that could be targeted in the development of new treatments to help the brain overcome glycolysis defects in Alzheimer's disease.
The research did not show that disruption in glucose metabolism in the brain was the only metabolic process connected to AD, but the team hopes to look into other pathways in the brain that could also be related. The video below has more information.
Sources: National Institute on Aging, Journal Alzheimer's and Dementia, Pittsburgh Post-Gazette
