- Abnormalities in
the way the brain breaks down glucose has now been linked with Alzheimer's
disease pathology and symptoms
disease pathology is characterized by beta-amyloid protein plaques and
- Lower rates of glycolysis (breakdown of
glucose) have been correlated to more plaques and tangles in the brains of
Alzheimer's patients and with the onset of disease symptoms.
the world's longest-running scientific studies of human aging called the
Baltimore Longitudinal Study of Aging (BLAS) has come out with an analysis
connecting the breakdown of glucose (glycolysis) in the brain to the pathology
or disease formation of Alzheimer's disease (AD), as well as to the onset of
AD' outward symptoms.
pathology is characterized by
signature beta-amyloid protein plaques and neurofibrillary tangles in the
‘A link found between glucose breakdown in the brain and Alzheimer’s disease may be a novel mechanism to develop new drugs to help the brain overcome glycolysis defects in Alzheimer’s disease.’
in Alzheimer's & Dementia: the Journal of the
says that there is evidence linking the
severity of the abnormalities in the brain's glycolysis to the severity of
Alzheimer's pathology. The research was supported by the National Institute on
Aging (NIA), part of the National Institutes of Health.
study was 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
Longitudinal Study of Aging (BLAS)
tissue samples from participants were analyzed at autopsy and the neurological,
physical and psychological data on participants were studied over several
belonged to three different disease status.
individuals who served as controls
who did not have any symptoms of AD during life but whose brain
post-mortem revealed significant levels of Alzheimer's pathology
with Alzheimer's symptoms during life and with confirmed AD pathology in
the brain at death
pathology is more pronounced in areas like the frontal and temporal cortex and
lesser in the cerebellum. When researchers measured glucose levels in these
different brain regions they found distinct abnormalities in glycolysis. Since
glycolysis is the primary process by which the brain breaks down glucose, lower
rates of glycolysis would directly correlate to higher levels of glucose in the brain.
showed that -
rates of glycolysis correlated to more severe plaques and tangles found in
the brains of people with the disease.
brain glycolysis reduces even more, it could have a direct effect on
the expression of symptoms of Alzheimer's disease during life, such as
problems with memory.
of enzymes (amino acids serine, glycine and alanine) controlling the key
glycolysis steps were lower in Alzheimer's cases compared to normal brain
enzyme activity was associated with more severe Alzheimer's pathology in
the brain and the development of symptoms.
measurement of cellular proteins (proteomics) revealed that the
levels of GLUT3, a glucose transporter protein, in neurons were lower in
brains with Alzheimer's pathology compared to normal brains.
increases in blood glucose levels in study participants taken years before
they died correlated with greater brain glucose levels at death.
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."
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.
Future plans for Thambisetty and his team
include studying other metabolic pathways linked to glycolysis to determine if
they show any abnormalities and how that could relate to Alzheimer's pathology
in the brain.
disease is a chronic neurodegenerative disease and is the cause of
60% to 70% of cases of dementia. The earliest symptom of the disease is
difficulty in remembering recent events. Advanced Alzheimer's can
include problems with language, easily getting lost, mood
swings, lack of motivation, not able to take care of themselves,
and behavioral issues. The patients later withdraw from family and society
and lose bodily functions; this ultimately leads to death. The average life
expectancy of AD patients following diagnosis is three to nine years.
- "Evidence for brain glucose dysregulation in Alzheimer's disease" by Yang An, Vijay R. Varma, Sudhir Varma, Ramon Casanova, Eric Dammer, Olga Pletnikova, Chee W. Chia, Josephine M. Egan, Luigi Ferrucci, Juan Troncoso, Allan I. Levey, James Lah, Nicholas T. Seyfried, Cristina Legido-Quigley, Richard O'Brien, and Madhav Thambisetty in Alzheimer's & Dementia:. Published online October 19 2017 doi:10.1016/j.jalz.2017.09.011
- Alzheimer's disease - (https://en.wikipedia.org/wiki/Alzheimer's_disease)