Sugar’s
“tipping point” link to Alzheimer’s disease revealed
University of Bath
For the first time a “tipping point” molecular link between the
blood sugar glucose and Alzheimer’s disease has been established by scientists,
who have shown that excess glucose damages a vital enzyme involved with
inflammation response to the early stages of Alzheimer’s.
Abnormally high blood sugar levels, or hyperglycaemia, is
well-known as a characteristic of diabetes and obesity, but its link to
Alzheimer’s disease is less familiar.
Diabetes patients have an increased risk of developing
Alzheimer’s disease compared to healthy individuals. In Alzheimer’s disease
abnormal proteins aggregate to form plaques and tangles in the brain which
progressively damage the brain and lead to severe cognitive decline.
Scientists already knew that glucose and its break-down products
can damage proteins in cells via a reaction called glycation but the specific
molecular link between glucose and Alzheimer’s was not understood.
But now scientists from the University of Bath Departments of
Biology and Biochemistry, Chemistry and Pharmacy and Pharmacology, working with
colleagues at the Wolfson Centre
for Age Related Diseases, King’s College London, have unraveled that
link.
By studying brain samples from people with and without Alzheimer’s using a sensitive technique to detect glycation, the team discovered that in the early stages of Alzheimer’s glycation damages an enzyme called MIF (macrophage migration inhibitory factor) which plays a role in immune response and insulin regulation.
MIF is involved in the response of brain cells called glia to
the build-up of abnormal proteins in the brain during Alzheimer’s disease, and
the researchers believe that inhibition and reduction of MIF activity caused by
glycation could be the ‘tipping point’ in disease progression. It appears that
as Alzheimer’s progresses, glycation of these enzymes increases.
The study is published in the journal Scientific Reports.
Professor Jean
van den Elsen, from the University of Bath Department of Biology and Biochemistry,
said: “We’ve shown that this enzyme is already modified by glucose in the
brains of individuals at the early stages of Alzheimer’s disease. We are
now investigating if we can detect similar changes in blood.
“Normally MIF would be part of the immune response to the
build-up of abnormal proteins in the brain, and we think that because sugar
damage reduces some MIF functions and completely inhibits others that this
could be a tipping point that allows Alzheimer’s to develop.
Dr Rob Williams,
also from the Department of Biology and Biochemistry, added: “Knowing this will
be vital to developing a chronology of how Alzheimer’s progresses and we hope
will help us identify those at risk of Alzheimer’s and lead to new treatments
or ways to prevent the disease.
Dr Omar Kassaar, from the University of Bath, added: “Excess
sugar is well known to be bad for us when it comes to diabetes and obesity, but
this potential link with Alzheimer’s disease is yet another reason that we
should be controlling our sugar intake in our diets.”
Globally there are around 50 million people with Alzheimer’s
disease, and this figure is predicted to rise to more than 125 million by 2050.
The global social cost of the disease runs into the hundreds of billions of
dollars as alongside medical care patients require social care because of the
cognitive effects of the disease.
The study is a collaboration between Dr Rob Williams and Prof
Jean van den Elsen in the Department of Biology & Biochemistry, Prof Tony James in
the Department of Chemistry and Prof Stephen
Ward in the Department of Pharmacy & Pharmacology.
It was funded by the Dunhill Medical
Trust. Human brain tissue for this study was provided through Brains
for Dementia Research, a joint initiative between Alzheimer’s Society and
Alzheimer’s Research UK in association with the Medical Research Council.