Diabetes gene linked to degeneration of enzyme involved in Alzheimer's disease onset and progression
Mount Sinai School of Medicine researchers have found that a gene associated with the onset of Type 2 diabetes also is found at lower-than-normal levels in people with Alzheimer's disease. The research, led by Giulio Maria Pasinetti, MD, PhD, The Saunder Family Professor in Neurology, and Professor of Psychiatry and Geriatrics and Adult Development at Mount Sinai School of Medicine, was published this month in Aging Cell.
The new study provides insight into a potential mechanism that might explain the relationship between Type 2 diabetes and the onset and progression of Alzheimer's disease. Recent evidence indicates that healthy elderly subjects affected by Type 2 diabetes are twice as likely to develop Alzheimer's disease, but researchers have been unable to explain how.
"The relationship between Type 2 diabetes and Alzheimer's disease has been elusive," said Dr. Pasinetti. "This new evidence is of extreme interest, especially since approximately 60 percent of Alzheimer's disease cases have at least one serious medical condition primarily associated with Type 2 diabetes."
Using mice that were genetically engineered to have Alzheimer's disease comparable to that seen in humans, Dr. Pasinetti and colleagues found that a gene known as proliferator-activated receptor coactivator 1 (PGC-1), a key regulator of glucose currently investigated as a potential therapeutic target for Type 2 diabetes, is decreased in Alzheimer's disease. The team reports that this decrease might be causally linked to promotion of Alzheimer's disease. They found that PGC-1 promotes degradation of a specific enzyme known as beta-secretase (BACE). ACE is directly involved in the processing and eventually generation of β-amyloid, an abnormal protein highly linked to Alzheimer's disease and brain degeneration.
"Our research is the first to find that PGC-1 is a common denominator between Type 2 diabetes and Alzheimer's disease," said Dr. Pasinetti. "This discovery will have significant implications for the more than five million Americans affected by Alzheimer's disease, a number that is expected to skyrocket in the next three decades as the population ages. We look forward to continuing to research this discovery and translate it into the development of novel approaches for disease prevention and treatment."
Dr. Pasinetti and his colleagues are optimistic that if they find that PGC-1 can be manipulated pharmacologically to prevent BACE accumulation in the brain, these studies will provide important insights for the formulation of novel treatments and possible preventative strategies in Alzheimer's disease.
