Biomarkers in Saliva May Spot Alzheimer's Early  

Megan Brooks

May 24, 2017

Results of a pilot study suggest that biomarkers in saliva may help identify people at risk for developing Alzheimer's disease (AD).

"Our results demonstrate that there are significant differences in the concentrations of a large number of salivary metabolites in patients with AD and mild cognitive impairment (MCI) relative to unaffected controls," they report.

The study was published online May 11 in the Journal of Alzheimer's Disease

"We used metabolomics, a newer technique, to study molecules involved in metabolism," Stewart Graham, PhD, from Oakland University–William Beaumont School of Medicine, Beaumont Health in Royal Oak, Michigan, explains in a statement. "Our goal was to find unique patterns of molecules in the saliva of our study participants that could be used to diagnose Alzheimer's disease in the earliest stages, when treatment is considered most effective."

The research team biochemically profiled saliva samples collected from 12 healthy controls, 8 individuals with MCI, and 9 with AD. "We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls," they report.  

The metabolites galactose, imidazole, and acetone; creatine and 5-aminopentanoate; and propionate and acetone were used to distinguish controls vs MCI, MCI vs AD, and controls vs AD, respectively.

Some of the observed variances in these biomarkers were "relatively large," the researchers say. Using logistic regression modeling, they achieved statistically significant prediction of MCI and AD from controls and MCI from AD.

The regression model with the greatest predictive ability was generated when controls were separated from MCI by using the concentrations of galactose, imidazole, and acetone with an area under the receiver-operating characteristic curve (AUC) of 0.826 (95% confidence interval [CI], 0.634 - 1.00) and with a sensitivity and specificity of 0.909 and 0.889, respectively.

When the concentration values of creatinine and 5-aminopentanoate from MCI and AD patients were analyzed by using logistic regression, an AUC value of 0.897 (95% CI, 0.707 - 1.000) was achieved, with a sensitivity and specificity of 0.900 and 0.944, respectively.

The logistic regression model based on the concentration values of propionate and acetone for separating controls from patients with AD produced an AUC of 0.871 (95% CI, 0.689 - 1.000) with 0.909 and 0.842 sensitivity and specificity values, respectively.

Of all the logistic regression models created, controls vs MCI was the weakest. "This could be the result of the heterogeneous nature of MCI; 10% of the MCI sufferers progress to AD while a small percentage regress to being considered healthy controls," the researchers note.

"The simple fact that we were able to use saliva to separate the groups was most interesting," Dr Graham noted in an interview with Medscape Medical News.

The main limitation of this pilot study is the small sample size. Nonetheless, it provides "preliminary evidence that salivary metabolites may be useful for AD biomarker development. Given the convenience and the frequency with which saliva can be obtained, larger studies are justified," the researchers conclude.

"We have already applied to the Alzheimer's Association to follow up with a larger study to see if we can validate our initial findings," said Dr Graham, adding, "I honestly do think there will be a saliva test for AD that will reach the clinic in the future."

Having a simple test for AD has major implications for therapeutic drug trials, he noted.  "The majority of clinical trials in Alzheimer's disease have failed because of mis-stratification of patients. If we are able to stratify patients into correct groups before they go into the trial, we might have a lot more success when we are targeting specific drugs," Dr Graham commented.

Search for Biomarker Important

In an interview with Medscape Medical News, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said, "one of the greatest needs for Alzheimer's right now is to find a valid biomarker of the disease that would identify patients way before they get sick, and this need is obviously coupled with finding a new treatment.

"This study from a single geriatric clinic in a small number of patients finds differences in saliva after doing an extensive metabolomic analysis. The chemistry of saliva is going to change in a wide variety of situations, so testing this in a larger sample and in a community sample would be the next step. This is a useful first step, and continued effort to try to find a biomarker is worthwhile and important," said Dr Iadecola, who wasn't involved in the study.

On that front, Dr Iadecola noted that phosphorylated tau in plasma is a "strong" candidate biomarker. "My feeling is that ultimately we are going to need a panel of biomarkers. Perhaps a blood test, in conjunction with a saliva test, in conjunction with amyloid imaging," he said.

Importantly, added Dr Iadecola, "efforts to develop biomarkers need to continue in parallel with therapeutic development because eventually you are going to need a biomarker to select patients for treatment."

The study was supported by the Fred A. and Barbara M. Erb Family Foundation. The authors have disclosed no relevant financial relationships.

J Alzheimer Dis. Published online May 11, 2017.  Abstract

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