The worldās first blood test to predict Alzheimerās 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 Alzheimerās decades earlier.
Globally, 35 million people are living with Alzheimerās. 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.
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 Alzheimerās or mild cognitive impairment, thought to be the earliest noticeable sign of dementia, including Alzheimerās disease.
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An analysis of the participantsā blood highlighted 10 metabolites that were depleted in those with mild cognitive impairment who went on to get Alzheimerās compared with those who didnāt. In subsequent trials, the team showed these chemicals could predict who would go on to get Alzheimerās 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. āWe think the decrease in these chemicals reflects the breakdown of neural populations in the brain,ā says team member 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 Alzheimerās. Mapstone says that it may even be able to predict the disease much earlier, because the brain changes associated with Alzheimerās begin many years before symptoms occur. āThese metabolic changes might occur 10 or 20 years earlier ā that would give us a real head start on predicting the disease,ā 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. āThe gene changes are linked to the metabolite changes, so weāre hoping to put all this together to provide a more complete description of the underlying pathology of the disease,ā he says. āWhatās 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.ā
Knowledge is power
But with no treatments available, would anyone want to take these tests?
Mapstone says yes. āIn my experience, the majority of people are very interested to know whether they will get Alzheimerās. They believe that knowledge is power ā particularly when it comes to your own health. We may not have any therapy yet but there are things we can do ā we can get our financial and legal affairs in order, plan for future care, and inform family members.ā
If the test could predict the disease 20 years before symptoms appear, the implications are huge, he says. āImagine 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.ā
āIn the short term, I think some people would want to know and some wouldnāt,ā says , 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 Alzheimerās by age 45 (see āTesting a drug for the memory curseā).
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 Alzheimerās in older people who donāt yet have memory problems but do have amyloid building up in their brain.
āIf an even earlier pre-clinical population could be identified with this blood test, it could be game changing,ā says Young-Pearse.
Journal reference: Nature Medicine, DOI:
Testing a drug for the memory curse
In Yarumal, Colombia, lives a unique population of people, many of whom have fallen ill with what some locals call La Bobera ā āthe foolishnessā. The disease that makes villagers confused before robbing them of their memories was once thought by some to be caused by a priest who cursed the villagers for stealing from his collection boxes. It is now known to be a form of early onset Alzheimerās, caused by a rare mutation in a gene called PSEN1. The town has the largest population of Alzheimerās sufferers in the world ā about 5000 people have the gene mutation, half of whom will be diagnosed with Alzheimerās by the age of 45.
This year at the University of Antioquia, Colombia, will begin a trial of an Alzheimerās drug ā called Crenezumab ā on Yarumulās inhabitants.
The team will be looking to see whether early intervention with the drug delays the onset of the disease, something that is hard to do in people without the genetic predisposition because so far it has been impossible to tell who will get the disease and who wonāt. āThese are prospective studies so weāll have to wait a while for the results but they will offer very important insights,ā says Mark Mapstone at the University of Rochester Medical Center in New York.
