Pauline Anderson

July 20, 2015

WASHINGTON, DC — A new Canadian study shows that metabolites in salivary samples may be able to discriminate normal aging from mild cognitive impairment (MCI) and Alzheimer's disease (AD) and can predict neurocognitive performance.

Contrary to currently used AD biomarkers, such as amyloid-β and tau, saliva is easy and cheap to collect and to transport. "Saliva, which is a noninvasive biofluid, holds much promise for Alzheimer's research," Shraddha Sapkota, MSc, a PhD student in the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada, told Medscape Medical News.

Shraddha Sapkota

Her research is in line with the focus on detecting AD as early as possible, but a routine saliva test is a long way from routine clinical practice. "We are at the very early stages and much more work is needed before we can predict when and if it will be used clinically," said Sapkota.

She presented the new results at a press briefing during the Alzheimer's Association International Conference (AAIC) 2015.

Biomarker Profiles

For this analysis, the researchers used data from the Victoria Longitudinal Study, a long-term investigation of human aging. The analysis included 35 persons with normal again, 25 with MCI, and 22 with AD.

For the study, researchers used "global metabolomics," which involves detecting and quantifying relative contributions of hundreds of metabolites, small molecules that are intermediate products, and end products of chemical reactions.

The metabolomics technique the researchers used involves liquid chromatography-mass spectrometry, which separates a mixture of compounds by quantifying each component and measuring the mass-to-charge ratio of charged particles.

From their metabolomics analysis, the researchers aimed to discover specific biomarker profiles that discriminate between normal aging, MCI, and AD. Another goal was to test top AD-related discriminative biomarkers for associations with pre-AD cognitive performance.

Previous pilot data using saliva from participants with normal aging and those with MCI had detected up to 1000 biomarkers, the top 18 of which discriminated between cognitive groups. The new data, said Sapkota, expands the number of detected biomarkers.

"We detected about 1500 to 6000 metabolites and only the top 6 to 12 clearly discriminated the three groups," she said. However, she and her colleagues don't know whether the biomarkers are related.

This type of analysis is usually done with blood or urine, "but the technology has allowed us to detect a larger number of metabolites in saliva, which is amazing," commented Sapkota.

The researchers were able to detect these newly identified biomarkers in a separate sample that included 10 patients with normal aging, 10 with MCI, and 7 with AD. "We found the same biomarkers in a validation sample," said Sapkota.

The researchers also found that these newly discovered biomarkers can predict differential cognitive performance. Upregulated metabolites had a higher concentration in the AD group than in the normal aging or MCI groups. As well, within the AD group, higher biomarker concentration predicted lower cognition.

Within the normal aging group, there was a "subtle but similar pattern," which Sapkota said suggests "early evidence of possible preclinical decline."

The challenge now is to see whether saliva-based biomarkers can predict different clinical manifestations of non-AD groups, she said. Sapkota noted that the connection or the mechanism linking the identified metabolites to cognition is still unclear.

Early Detection

The new research results add weight to the idea that AD risk can be detected early both in persons with MCI and in those with normal aging. As well, the ease at which saliva can be collected opens the door to including participants in remote areas into these types of studies, she said.

The next research step for her and her colleagues will involve collecting saliva from a larger sample size, and perhaps also studying the associations longitudinally.

"The content of saliva changes based on whether it's collected today or tomorrow, and within hours, it could change," said Sapkota.

William Klunk, MD, PhD, chair, Alzheimer's Association medical and scientific advisory council, and co-director, Alzheimer Disease Research Center, University of Pittsburgh Medical Center, Pennsylvania, who moderated the press conference here, likened AD biomarkers to the selection of items in a toolbox; Some are good for doing fast jobs while others are more expensive but perhaps more accurate.

What's exciting about a possible saliva test is that it's relatively inexpensive and noninvasive, said Dr Klunk. "The question is, can we bring the sensitivity and specificity, the overall accuracy of the test, closer to the more invasive tests?"

More sensitive tests include measures of amyloid-β and tau in cerebral spinal fluid or positron emission tomographic measures of amyloid in the brain.

"What we struggle with is how to get a good test," said Dr Klunk. "The perfect test would be 100% sensitive to the disease so whenever it was positive, it would be 100% correct that it was that disease and not another, and it would be inexpensive, and easy for a person to get tested."

It's conceivable that the saliva test is such a perfect test, and it's "foreseeable" that in future such a test might be available not only at the doctor's office but also conveniently at the mall, along with blood pressure tests, said Dr Klunk.

The study was funded by grants from the Canadian Institutes of Health Research and the National Institutes of Health.

Alzheimer's Association International Conference (AAIC) 2015. Poster 4782. Presented July 19, 2015.


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