Alzheimer's, Dementia & Mental Health
Researchers on Path to Discover Link Between
Diabetes and Alzheimer’s Disease
Mount Sinai researchers discover novel mechanisms
that might causally link type-2 diabetes to Alzheimer's
April 10, 2009 – Previous research has found that
healthy elderly people with type-2 diabetes are twice as likely to
develop Alzheimer’s disease, but the link that increases this risk has
been a mystery. In a new report, however, researchers from Mount Sinai
School of Medicine have found a gene that may be involved.
A recent study by Mount Sinai faculty suggests that
a gene associated with onset of type-2 diabetes also decreases in
Alzheimer's disease dementia cases. The research, led by Dr. Giulio
Maria Pasinetti, MD, Ph.D., The Aidekman Family Professor in Neurology,
and Professor of Psychiatry and Geriatrics and Adult Development at
Mount Sinai School of Medicine, was published this week in the
scientific journal, Archives of Neurology.
"This new evidence is of extreme interest," Dr.
Pasinetti tells us, "especially because of the evidence that
approximately 60% of Alzheimer's disease dementia cases have at least
one serious medical condition primarily associated with type-2 diabetes,
a chronic condition which includes high blood glucose content
(hyperglycemia) and reduced sensitivity to insulin, among other
conditions."
"The relationship between type-2 diabetes and
Alzheimer's disease is elusive," says Dr. Pasinetti.
Not all subjects with type-2 diabetes are affected
by Alzheimer's disease, and similarly, not all Alzheimer's disease cases
are diabetic. However, in the last few years, epidemiological evidence
indicates that, relative to healthy elderly subjects, people of the same
age affected by type-2 diabetes are twice as likely to develop
Alzheimer's disease dementia. The reason is not known.
The new study from Dr. Pasinetti provides insight
into a potential mechanism that might explain the relationship between
type-2 diabetes and Alzheimer's disease onset and progression.
Dr. Pasinetti and colleagues found that a gene
known as proliferator-activated receptor coactivator 1 - (PGC-1 ), a key
regulator of glucose content currently investigated as a potential
therapeutic target for type-2 diabetes, is also decreased in Alzheimer'
disease dementia cases.
Most importantly, Dr. Pasinetti reports that PGC-1
decreased in Alzheimer' disease dementia cases with progression of the
clinical disease and positively correlates with brain accumulation of
β-amyloid, an abnormal protein highly linked to Alzheimer' disease
dementia and brain degeneration.
This evidence is of high interest to the field and
suggests, for the first time, a strong relationship between decreased
content of a gene responsible for type-2 diabetes in Alzheimer's disease
dementia cases, says Dr. Pasinetti.
"Of considerable interest," continues Dr. Pasinetti,
"is the evidence found in further mechanistic studies in our laboratory,
indicating that promoting PGC-1 content in brain cells, using a
transgenic mouse model of Alzheimer's disease, attenuates
hyperglycemic-mediated production of β-amyloid, highly linked to
Alzheimer' disease dementia. These findings are very exciting, and for
the first time tentatively link type-2 diabetic metabolic defects to
increasing dementia mediated by β-amyloid production."
The discovery in Dr. Pasinetti's laboratory has
staggering societal implications: there are currently more than 5
million Americans affected by Alzheimer's disease dementia, and the
disease incidence is expected to skyrocket in the three decades as the
population ages. The question now is how we can translate this evidence
into the development of novel approaches for disease prevention and
treatment.
Dr. Pasinetti and his colleagues are optimistic
that if they find that PGC-1α can be manipulated pharmacologically,
these studies will provide important insights to be used in the
formulation of novel treatments and possible preventative strategies in
Alzheimer's disease.
Information Source
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses The
Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai
Hospital is one of the nation's oldest, largest and most-respected
voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed
tertiary-care teaching facility that is internationally acclaimed for
excellence in clinical care. Last year, nearly 50,000 people were
treated at Mount Sinai as inpatients, and there were nearly 450,000
outpatient visits to the Medical Center. Mount Sinai School of Medicine
is internationally recognized as a leader in groundbreaking clinical and
basic-science research, as well as having an innovative approach to
medical education. With a faculty of more than 3,400 in 38 clinical and
basic science departments and centers, Mount Sinai ranks among the top
20 medical schools in receipt of National Institute of Health (NIH)
grants.
