Higher brain glucose levels may mean more severe Alzheimer's

November 6, 2017, National Institutes of Health
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

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 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.

"For some time, researchers have thought about the possible links between how the brain processes glucose and Alzheimer's," said NIA Director Richard J. Hodes, M.D. "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."

While similarities between diabetes and Alzheimer's have long been suspected, they have been difficult to evaluate, since insulin is not needed for glucose to enter the brain or to get into neurons. The team tracked the brain's usage of glucose by measuring ratios of the amino acids serine, glycine and alanine to glucose, allowing them to assess rates of the key steps of glycolysis. They found that the activities of enzymes controlling these key glycolysis steps were lower in Alzheimer's cases compared to normal brain tissue samples. Furthermore, lower enzyme activity was associated with more severe Alzheimer's pathology in the brain and the development of symptoms.

Next, they used proteomics - the large-scale measurement of cellular proteins - to tally levels of GLUT3, a glucose transporter protein, in neurons. They found that GLUT3 levels were lower in brains with Alzheimer's pathology compared to normal brains, and that these levels were also connected to the severity of tangles and plaques. Finally, the team checked in study participants years before they died, finding that greater increases in blood glucose levels correlated with greater brain at death.

"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," said Thambisetty.

The researchers cautioned that it is not yet completely clear whether abnormalities in brain metabolism are definitively linked to the severity of Alzheimer's disease symptoms or the speed of disease progression. The next steps for Thambisetty and his team include studying abnormalities in other metabolic pathways linked to glycolysis to determine how they may relate to Alzheimer's pathology in the brain.

Explore further: Lower brain glucose levels found in people with obesity, type 2 diabetes

More information: Yang An et al. Evidence for brain glucose dysregulation in Alzheimer's disease, Alzheimer's & Dementia (2017). DOI: 10.1016/j.jalz.2017.09.011

Related Stories

Lower brain glucose levels found in people with obesity, type 2 diabetes

October 19, 2017
Glucose levels are reduced in the brains of individuals with obesity and type 2 diabetes compared to lean individuals, according to a new Yale study. The finding might explain disordered eating behavior—and even a higher ...

Abnormal brain protein may contribute to Alzheimer's disease development

September 30, 2016
A recently-recognized pathologic protein in the brain may play a larger role in the development of clinical Alzheimer's disease dementia than previously recognized, according to a study by researchers at Rush University Medical ...

Brain fatty acid levels dysregulated in Alzheimer's disease

March 21, 2017
The concentration of six unsaturated fatty acids in key brain regions are associated with Alzheimer disease (AD) cognitive symptoms and neuropathology, according to a study publishing in PLOS Medicine.

Alzheimer's may affect the brain differently in African-Americans than European-Americans

July 15, 2015
Alzheimer's disease may cause different changes in the brain, or pathologies, in African-Americans than in white Americans of European descent, according to a study published in the July 15, 2015, online issue of the medical ...

Diabetes drug could influence brain activity in Alzheimer's

April 28, 2016
Researchers in Denmark have released findings from a small clinical trial of the diabetes drug liraglutide in people living with Alzheimer's disease.

Alzheimer's disease study links brain health and physical activity

June 22, 2017
People at risk for Alzheimer's disease who do more moderate-intensity physical activity, but not light-intensity physical activity, are more likely to have healthy patterns of glucose metabolism in their brain, according ...

Recommended for you

Genes linked to Alzheimer's contribute to damage in different ways

June 12, 2018
Multiple genes are implicated in Alzheimer's disease. Some are linked to early-onset Alzheimer's, a condition that develops in one's 30s, 40s and 50s, while others are associated with the more common late-onset form of the ...

Researchers reverse cognitive impairments in mice with dementia

June 8, 2018
Reversing memory deficits and impairments in spatial learning is a major goal in the field of dementia research. A lack of knowledge about cellular pathways critical to the development of dementia, however, has stood in the ...

As mystery deepens over the cause of Alzheimer's, researchers seek new answers

June 6, 2018
For more than 20 years, much of the leading research on Alzheimer's disease has been guided by the "amyloid hypothesis."

Research reveals how Tau aggregates can contribute to cell death in Alzheimer's disease

June 5, 2018
New evidence suggests a mechanism by which progressive accumulation of Tau protein in brain cells may lead to Alzheimer's disease. Scientists studied more than 600 human brains and fruit fly models of Alzheimer's disease ...

How does alcohol influence the development of Alzheimer's disease?

June 4, 2018
Research from the University of Illinois at Chicago has found that some of the genes affected by alcohol and inflammation are also implicated in processes that clear amyloid beta—the protein that forms globs of plaques ...

Dementia patients could remain at home longer thanks to ground breaking technology

June 4, 2018
Innovative new technology will enable people with dementia to receive round the clock observation and live independently in their own homes, a new study in the Journal PLOS One reports.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.