Your spit might just reveal whether you’re a likely candidate for developing Alzheimer’s disease.
That at least is the hope of Canadian researchers whose study suggests that analyzing certain chemical compounds in saliva could provide a cheap, noninvasive way to learn whether the brain has begun to undergo the changes that culminate in loss of memory and cognitive function.
Their study was one of several on the hunt for new biomarkers that were presented Sunday of the first day of the five-day Alzheimer’s Association International Conference in the District. Other biomarker research looked at the possibility of analyzing brain fluid for the elevated presence of neurogranin, a protein that is found only in the brain and plays an important role in conducting signals between the synapses of nerve cells, or using PET scans to identify inflammation, which can be fatal for brain tissue.
The scientific gathering — which is expected to draw nearly 4,500 researchers from around the world — comes as several developed nations shift toward older populations. More than 5 million people are living with Alzheimer’s in the United States, a number expected to increase to 13.5 million by 2050.
With about 10,000 baby boomers turning 65 every day, Alzheimer’s researchers and their advocates say the United States needs to step up the search for a cure or treatments before the costs to family caregivers and the federal government, through Medicare, begin to soar. A step forward means finding ways to diagnose the disease better, particularly in its early stages before symptoms appear. And it also is likely to involve a multi-pronged approach.
Among other presentations Sunday, for example, neurologists at New York University’s School of Medicine unveiled data on a new class of drugs that target misfolded proteins, a biological phenomenon that is common to several neurodegenerative diseases. Fernando Goni, an adjunct professor at NYU’s Neurology Department, said new data suggest a class of monoclonal antibodies that home in on misshapen proteins such as amyloid beta and tau — both of which are distinguishing features of Alzheimer’s — as well as abnormal proteins found in people with Lewy body dementia or Parkinson’s disease.
A lot of attention was also given to the search for new, reliable biomarkers of Alzheimer’s disease. Because the preclinical stage of Alzheimer’s can last as long as 20 years, scientists are devoting more attention to finding ways that could determine whether a person is at risk well before memory loss or cognitive impairment occurs.
The ability to develop easy screening methods for them could allow doctors to intervene in ways to someday delay or prevent the onset of dementia. It is also key to enhancing pharmaceutical research, as drug companies are especially interested in identifying people at risk and enrolling them in clinical trials to test the efficacy of possible treatments.
In recent years, scientists have reported discoveries on a number of possible biomarkers linked to Alzheimer’s-related changes in the brain. Some might involve nothing more invasive than an eye scan or a skin test. But the test papers have been more hopeful than results.
On Sunday, Shraddha Sapkota, a neuroscience graduate student at the University of Alberta, said her team studied the presence in saliva of metabolites — which are molecular byproducts of metabolism — to see whether they could be a reliable early indicator of metabolism changes in the brain that also signal the early stages of Alzheimer’s disease.
Using liquid chromatography-mass spectrometry to analyze the samples, the researchers distinguished between groups of participants who were aging normally, suffering from mild cognitive impairment, or already diagnosed with Alzheimer’s. Sapkota said her team also found that higher levels of specific metabolites in the saliva also correlated to evidence of declining cognitive abilities.
“So that’s promising. What that does is it tells a physician in a regular doctor’s office that this person should get more testing,” said Maria C. Carrillo, chief science officer at the Alzheimer’s Association.
Other scientists were more cautious. Creighton H. “Tony” Phelps, director of the National Institute on Aging’s Alzheimer’s Disease Centers program, said it would be wonderful if doctors could eventually ask someone to spit in a cup or submit to an oral swab and determine whether the person is at greater risk for dementia. But the research seemed preliminary, he said.
“The idea is good. And I hope someday we’ll be able to do that. But we’ve had very bad luck with these panels of biomarker,” Phelps said.
Marilyn Albert, director of the Division of Cognitive Neuroscience at Johns Hopkins University’s Department of Neurology, presented a briefing Sunday that her team assessed a variety of current diagnostic tools and found that about six measures were particularly useful in predicting which cognitively normal people would develop Alzheimer’s within five years. Among the most useful measures were the Digit Symbol and Paired Associates Immediate Recall tests, which measure memory and cognition; analyzing cerebrospinal fluid for the presence of amyloid beta and tau, which are the two abnormal proteins that distinguish the presence of Alzheimer’s; and MRI scans that assess the volume or thickness, respectively, of the hippocampus and the right entorhinal cortex, which are parts of the brain critical to memory.
In another attempt to discover new biomarkers, a Dutch team of scientists explored the link between Alzheimer’s and a protein involved in sending messages between brain cells. Charlotte E. Teunissen, a researcher at the VU Medical Center in Amsterdam, said her team investigated neurogranin as a possible new biomarker for early detection of Alzheimer’s.
Though its properties are not fully understood, neurogranin plays an important role in helping neurons communicate between synapses. Using samples of cerebrospinal fluid – a clear liquid that acts as a biological and mechanical buffer for the brain and spinal cord – scientists found that neurogranin levels were significantly higher for people with Alzheimer’s disease than with people who were cognitively normal.
The researchers used needles to draw two samples of cerebrospinal fluid from the backs of 163 people, including 37 who were cognitively normal, 61 who were showing signs of mild cognitive impairment and 65 who had been diagnosed with Alzheimer’s.
The participants gave two cerebrospinal fluid samples, each about two years apart. The researchers found that higher levels of neurogranin in people with Alzheimer’s. Rising levels of neurogranin also predicted progression from mild cognitive impairment to dementia. The levels were also correlated with the presence of tau and ptau-181, which are proteins linked to Alzheimer’s disease.
Bastian Zinnhardt, a researcher with the University of Muenster and the European Institute for Molecular Aging, presented research that suggested that positron emission tomography (PET) scans could target inflammation in the brain as a possible telltale early sign of Alzheimer’s — and perhaps someday open pathways to a Trojan Horse-like method of treating the disease.
The scans, using radioactive compounds that bind with receptors or other targets in the brain, were used to home in on microglial cells. Microglial cells are immune bodies that operate in the brain as a kind of free-floating army of demolition crews and garbage collectors. Some of them have the ability either to trigger an inflammatory response or inhibit inflammation. Some of them can, in effect, either kill brain cells or protect them.
Until now, however, PET scans have only been able to target a protein produced at elevated levels by activated microglial cells. But it’s been difficult to target the specific types of microglial that either protect or harm brain tissue, Zinnhardt said.
But by identifying new target receptors on the microglial cells, Zinnhardt’s team appears closer to being able to distinguish between the good guys and the bad guys, potentially opening the way to identifying treatments to restore the balance between the two.
Phelps said finding inflammation in specific areas of the brain that are linked to memory and cognition could serve as a useful biomarker of Alzheimer’s. But he also said the chemical compounds that help illuminate those areas of inflammation could also be tweaked and used to send in chemicals that wouuld bind with those microglial cells and, depending on whether they were friend or foe, either boost them or destroy them.