For the first time, scientists have found a connection between abnormalities in how the brain breaks down glucose and the severity of the signature amyloid plaques and tangles in the brain, as well as the onset of eventual outward symptoms, of Alzheimer’s disease. The study was supported by the National Institute on Aging (NIA), part of the National Institutes of Health, and appears in the Nov. 6, 2017, issue of Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association.
Led by Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience, researchers looked at brain tissue samples at autopsy from participants in the Baltimore Longitudinal Study of Aging (BLSA), one of the world’s longest-running scientific studies of human aging. The BLSA tracks neurological, physical and psychological data on participants over several decades.
Researchers measured glucose levels in different brain regions, some vulnerable to Alzheimer’s disease pathology, such as the frontal and temporal cortex, and some that are resistant, like the cerebellum. They analyzed three groups of BLSA participants: those with Alzheimer’s symptoms during life and with confirmed Alzheimer’s disease pathology (beta-amyloid protein plaques and neurofibrillary tangles) in the brain at death; healthy controls; and individuals without symptoms during life but with significant levels of Alzheimer’s pathology found in the brain post-mortem.
They found distinct abnormalities in glycolysis, the main process by which the brain breaks down glucose, with evidence linking the severity of the abnormalities to the severity of Alzheimer’s pathology. Lower rates of glycolysis and higher brain glucose levels correlated to more severe plaques and tangles found in the brains of people with the disease. More severe reductions in brain glycolysis were also related to the expression of symptoms of Alzheimer’s disease during life, such as problems with memory.
