The world's first blood test to
predict Alzheimer's disease before symptoms occur has been developed. The test
identifies 10 chemicals in the blood associated with the disease two to three
years before symptoms start, but it might be able to predict Alzheimer's
decades earlier.
Globally, 35 million people are
living with Alzheimer's. It is characterised by a toxic build up of amyloid and
tau proteins in the brain, which destroys the neurons. Several blood tests can
diagnose the disease, but until now, none has had the sensitivity to predict
its onset.
Howard Federoff at Georgetown
University in Washington DC and his colleagues studied 525 people aged 70 and
over for five years. The group showed no signs of mental impairment at the
start of the study. Each year, the team performed a detailed cognitive
examination and took blood samples from all the participants. During this time,
28 people developed Alzheimer's or mild cognitive impairment, thought to be the
earliest noticeable sign of dementia, including Alzheimer's disease.
An analysis of the participants'
blood highlighted 10 metabolites that were depleted in those with mild
cognitive impairment who went on to get Alzheimer's compared with those who
didn't. In subsequent trials, the team showed these chemicals could predict who
would go on to get Alzheimer's within the next three years with up to 96 per
cent accuracy.
Decades of warning?
The 10 metabolites play a key role
in supporting cell membranes, maintaining neurons or sustaining energy processes.
"We think the decrease in these chemicals reflects the breakdown of neural
populations in the brain," says team member Mark Mapstone at the
University of Rochester Medical Center in New York.
Once verified in a larger group,
the test should provide a cheap and quick way of predicting Alzheimer's.
Mapstone says that it may even be able to predict the disease much earlier,
because the brain changes associated with Alzheimer's begin many years before
symptoms occur. "These metabolic changes might occur 10 or 20 years
earlier – that would give us a real head start on predicting the disease,"
he says.
The team is hoping to investigate
this by looking back at other dementia studies in which blood has been taken
over decades and seeing whether the chemical changes can be detected that
early, says Federoff.
The group also analysed the full
genome sequence of all of the participants in the study. That work has yet to
be published, but Federoff says the changes in genes over the five years of the
study are even more powerful than the metabolites at predicting who will
develop dementia. "The gene changes are linked to the metabolite changes,
so we're hoping to put all this together to provide a more complete description
of the underlying pathology of the disease," he says. "What's most
exciting is that we know the function of all the affected genes so if we can
intercept these changes, they might make good candidates for new drugs."
Knowledge is power
But with no treatments available,
would anyone want to take these tests?
Mapstone says yes. "In my
experience, the majority of people are very interested to know whether they
will get Alzheimer's. They believe that knowledge is power – particularly when
it comes to your own health. We may not have any therapy yet but there are
things we can do – we can get our financial and legal affairs in order, plan
for future care, and inform family members."
If the test could predict the
disease 20 years before symptoms appear, the implications are huge, he says.
"Imagine what you would do in your early 40s to slow the onset of the
disease. You could eat the right foods, avoid head trauma or do
more exercise."
"In the short term, I think
some people would want to know and some wouldn't," says Tracy
Young-Pearse, a neurologist at Harvard Medical School. However, if treatments
are developed that are only effective before neurons have started dying in
large numbers, then it will be an easy decision to choose to take the blood
test, she says.
Meanwhile, the new test will be
valuable for drug discovery efforts, she says. Years of failed drugs trials
have shown that you have to catch the disease early to have any influence.
Three studies starting this year
hope to do just that. One will test anti-amyloid drugs on healthy people with a
rare mutation that gives them early onset Alzheimer's by age 45 (see
"Testing a drug for the memory curse").
The second will take advantage of
a chemical developed last year that can be injected into the body and which accumulates
in tau tangles. It will allow researchers to track the progression of tau in
the living brain.
A third trial will investigate
whether anti-amyloid drugs can prevent Alzheimer's in older people who don't
yet have memory problems but do have amyloid building up in their brain.
"If an even earlier
pre-clinical population could be identified with this blood test, it could be
game changing," says Young-Pearse.
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