Low Brain Glucose Utilization May Be Early Sign of Alzheimers
Glucose is the preferred fuel for the brain, using 25% of total body stores. Researchers at Mount Sinai School of Medicine have found that patients with Alzheimer’s disease have lower glucose utilization in the brain than those with normal cognitive function , and that the decreased levels may be detectable up to 20 years prior to the first symptoms of the disease.
Using mice modified to develop Alzheimer’s disease, a research team led by Giulio M. Pasinetti MD PhD found that when beta amyloid proteins become detectable in the brain, the mitochondria of the cell where glucose is converted into energy became impaired. Within the equivalent of approximately 20 human years, the mice with decreased energy metabolism developed signs of Alzheimer’s disease, including cognitive deficits and impairment of the synaptic terminal, the area of the brain essential in memory formation.
"This new evidence could revolutionize the way we design interventions," said Merina T. Varghese, MD, co-author of the study and Postdoctoral Fellow in Neurology at Mount Sinai School of Medicine. "This study sets the stage for the development of potential novel preventions or therapies to apply in humans, even when they have normal cognitive function, to prevent the eventual onset of Alzheimer's disease."
In 2003, researchers in Germany noted that neuronal glucose metabolism and its control by the insulin signal transduction cascade are main components of the complex cellular and molecular processes that control memory formation and retrieval. Damage to any of the components that are involved in neuronal glucose metabolism cause disturbances in memory function, as is found in sporadic Alzheimer’s disease.
Abnormal brain glucose regulation may also affect conditions such as diabetes, stroke, schizophrenia and substance abuse tendencies.
"This evidence in mice validates that the diagnosis of probable Alzheimer's disease may be the end result of impairment in brain cell energy production," said Dr. Pasinetti, a Professor in Neurology and Psychiatry, Geriatrics, and Adult Development at Mount Sinai. "Identifying that mitochondrial impairment is evident years earlier than cognitive defects is a major breakthrough."
Translational Neuroscience, Volume 2, Number 1, 1-5, DOI: 10.2478/s13380-011-0011-8