Increased brain glucose may be associated with more severe Alzheimer’s symptoms

Written by Rhiannon Finnie

A recent study has reported a potential association between abnormalities in the mechanism of glucose metabolism in the brain with severity of amyloid plaques and neurofibrillary tangles, pathologies specific to Alzheimer’s disease.
Additionally, it reported an association between glucose metabolism and the eventual onset of outward symptoms of Alzheimer’s. This study, which was recently published in Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association, was supported by the National Institute on Aging (NIA) – a part of the National Institutes of Health (MD, USA).

Madhav Thambisetty, Head of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience, and his team investigated glucose levels in brain tissue samples from three groups of participants of the Baltimore Longitudinal Study of Aging. These groups were divided into: participants with Alzheimer’s symptoms during life and confirmed Alzheimer’s disease pathology in the brain at post-mortem; individuals without symptoms during life but with significant levels of Alzheimer’s pathology in the brain post-mortem; and healthy controls. The research focused on the frontal and temporal cortexes, areas considered vulnerable to Alzheimer’s pathology, comparing with the cerebellum, an area considered resistant to such pathological changes in relation.

Distinct abnormalities in glycolysis, the main mechanism of glucose metabolism in the brain, were discovered by the team. They observed that lower rates of glycolysis and higher brain glucose levels correlated to more severe amyloid plaques and neurofibrillary tangles in the brains samples from participants with the disease pathology. Severe reductions in brain glycolysis were also reported to be associated with the expression of symptoms of Alzheimer’s disease during life.

Richard J Hodes, Director of the NIA, explained: “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.”

It was reported that the activity rates of enzymes controlling key glycolysis steps were lower in samples positive for Alzheimer’s pathology. This lower enzyme activity was associated with more severe Alzheimer’s pathology in the brain and development of symptoms also.

To conclude, the team analyzed blood glucose levels of the participants in the years preceding their deaths, discovering that greater increase in blood glucose levels correlated with greater brain glucose levels at death.

Madhav Thambisetty summarized: “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.”

However, he also noted that the associations reported in the team’s recent research have not yet been confirmed and further research is required. Thambisetty and his team intend to continue researching abnormalities in other metabolic pathways linked to glycolysis in order to determine how they may relate to Alzheimer’s pathology.

Sources: Yang A, Vijay VR, Sudhir V et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. doi:10.1016/j.jalz.2017.09.011 (2017) (Epub ahead of print);