By Keith Mulvihill
NEW YORK, Jul 20 (Reuters Health) - Medical researchers at the University of
Virginia Health Systems report a direct link between abnormal mitochondria genes
and the amyloid proteins that cause brain cell damage and cell death in
Alzheimer's disease.
Found in most cells, mitochondria are responsible for energy production.
They carry within them pieces of circular DNA, and researchers note that
mitochondrial DNA is passed from mother to child. Abnormalities in mitochondrial
DNA have been associated with rare brain diseases, but the University of
Virginia team is the first to uncover a link between this DNA and Alzheimer's.
Alzheimer's disease is the most prevalent neurodegenerative disease. One of
the primary characteristics of Alzheimer's disease is a build-up of plaques made
of beta-amyloid protein in the brain.
While most of the research on Alzheimer's disease has focused on the type of
Alzheimer's that is familial, meaning it is inherited, this type roughly
accounts for only 10% of those with the disease. The other 90% of people who
develop Alzheimer's have what doctors call sporadic type Alzheimer's.
"Our studies have been devoted to the study of abnormal mitochondrial
functions and how that relates to sporadic Alzheimer's disease," said Dr. James
P. Bennett, Jr., a neurologist at the University of Virginia Health System in
Charlottesville.
"We accomplished this by developing cell models, called cybrid cells, where
we inserted mitochondrial genes from people with sporadic Alzheimer's disease
and people who do not suffer from Alzheimer's disease--this group of cells acted
as the 'control.' We then compared what happened in the two different types of
cells."
The investigators found that the cells from Alzheimer's patients contained
twice as much amyloid protein as the nondiseased cells.
"The importance of this particular paper is that the work we did with the
cybrid cells show how the cells oversecrete the beta-amyloid proteins," Bennett
said.
The researchers then traced backwards, through the cell mechanism, learning
how the cells physically oversecrete the two common amyloid proteins. In
addition, the researchers learned that cell death pathways were activated to a
greater degree in diseased cells.
"By introducing mitochondrial genes from Alzheimer's patients you end up
damaging mitochondrial activity and in turn activating the cell death cascade,"
said Bennett in an interview with Reuters Health. "The cell death mechanism then
drives the cell in the oversecretion and depositing of the amyloid proteins," he
added.
"Our research is the first to define an actual mechanism as to how
mitochondria genes from sporadic Alzheimer's disease result in oversecretion and
deposition of amyloid proteins, specifically AB (I-40) and (I-42) peptides,"
Bennett explained. "We have a cell model that is tied directly to what happens
in actual patients' brains with Alzheimer's disease."
Cell models are frequently used to screen drugs that could interrupt the
disease process. In the case of this particular Alzheimer's model, researchers
hope that drugs might one day be tested that would inhibit the amyloid secretion
process.
This week, Reuters Health reported that the National Institutes of Health
will spend $50 million over 5 years to accelerate research on Alzheimer's
disease. President Clinton also said that the number of Americans with
Alzheimer's is expected to more than triple by 2050. Currently, 1 in 10 people
over the age of 65, and as many as 50% of those over the age of 85 have
Alzheimer's disease.
