Saliva Test for Alzheimer's?

December 01, 2016

Canadian researchers have developed a simple saliva test for the diagnosis of Alzheimer's disease, which they say may also be used to identify individuals at high risk of developing the condition in future.

The test is based on detecting levels of amyloid β42 (Aβ42), a peptide fraction of amyloid-β protein precursor.

In a paper published online in the Journal of Alzheimer's Disease, the researchers, from Aurin Biotech Inc Ltd, Vancouver, British Columbia, Canada, describe studies they say show that Aβ42 is continuously being generated throughout the body and is secreted into the saliva as well as other tissues and bodily fluids.

They report results from a test that they say correlates levels of Aβ42 in the saliva of persons with Alzheimer's or those at risk for the disease.

"We found that Aβ42 levels stayed the same from age 15 to 92 in controls, but patients with Alzheimer's had levels at least twice as high," coauthor Dr Patrick McGeer, president and CEO of Aurin Biotech, commented to Medscape Medical News. "Also, three individuals believed to be predestined to develop Alzheimer's — due to a gene mutation in one and strong family history in the other two — also had high levels of Aβ42 in their saliva similar to Alzheimer's cases."

The researchers report that saliva samples were first stabilized by adding thioflavin S as an antiaggregation agent and sodium azide as an antibacterial agent. Levels of Aβ42 were then measured with enzyme-linked immunosorbent assay-type tests.

The paper reports results of the test in 37 individuals: 7 patients with established Alzheimer's disease and 30 volunteers without Alzheimer's (age 16 to 92 years).

One of the non-Alzheimer's volunteers was cognitively normal but carried the presenilin 1 (PS-1) mutation, believed to predispose to Alzheimer's disease.

Results showed that 27 of the 30 non-Alzheimer's individuals showed almost identical levels of salivary Aβ42 (mean, 22.06 pg/mL) regardless of sex or age. All patients with Alzheimer's disease secreted levels of Aβ42 more than double those of controls (mean, 59.07 pg/mL).

The patient with the PS-1 mutation showed a level similar to that of the patients with Alzheimer's disease (60.90 pg/mL), which the researchers say "validat[es] the predictive capacity of the saliva test."

In addition, two participants without Alzheimer's had high saliva levels of Aβ42 , and both these individuals had mothers and other relatives affected by AD, "so they were known to be at a high risk to develop the disease."

"Overall, the data demonstrate that [Alzheimer's disease] can be diagnosed as well as predicted on the basis of salivary Aβ42 levels," the authors state.

Dr McGeer said, "These results need to be confirmed by others but they are very promising. The number of cases studied is small, but our results are so remarkable, we felt they should be made widely available. This saliva test is easy, non-invasive and accessible. Everyone should take it."

He added: "The only way that Alzheimer's added disease is going to be eliminated is to intervene at the earliest point well before symptoms develop. We need a test that detects what's happening in the brain many years before symptoms start to manifest. If you wait until symptoms develop that's far too late."

He maintains that Alzheimer's disease could be prevented in susceptible individuals "by a multifactorial approach including taking NSAIDs [nonsteroidal anti-inflammatory drugs], drinking coffee, doing exercise, and eating a Mediterranean diet. Such a regimen could dramatically spare individuals from Alzheimer disease if commenced well before the age of onset."

"We believe that a teaspoon of saliva can predict an individual's chances of getting Alzheimer's disease, and that once you know your chances you can take early preventive measures," added Dr McGeer.

Some Words of Caution

David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, commented on the study for Medscape Medical News.

"A noninvasive, inexpensive and accurate test for Alzheimer pathology that didn't require a lumbar puncture or PET [positron emission tomography] scan is a prized goal in the field. So it is exciting to see groups taking novel approaches," he said. "However, in taking such an assay from feasibility to reality is a lot of work, and the current report must be put in that context."

He added that the observations seen in this study "should definitely prompt more work and study to determine if the sensitivity, specificity, test-retest reliability and other features of the assay actually are suitable."

"The question comes down to whether the peripheral measurement of Aβ42 is sufficiently sensitive for Alzheimer's disease and at what level of disease (preclinical, early symptomatic or severe), and how specific it is. It would be exciting to see this test applied in one of the larger epidemiological studies where amyloid imaging or CSF [cerebral spinal fluid] assays for amyloid protein."

He also noted that it will be important to find out if the assay is "scalable" to other settings. "Is it so tricky to use that one laboratory's results don't replicate in another — that is the problem with the current CSF assay for Aβ42 now."

Also commenting for Medscape Medical News, representatives from the major Alzheimer's professional associations in both the United States and United Kingdom voiced similar opinions.

Keith Fargo, PhD, director of scientific programs and outreach at the US Alzheimer's Association, said, "This study appears to be a step forward in the quest to find the holy grail of an inexpensive, portable, noninvasive and accurate test for Alzheimer's which is also suggested to have potential for predicting who may develop the disease."

But Dr Fargo cautioned that numbers were small and the individuals classified as "predestined" to develop Alzheimer's were identified retrospectively. "While this is a very interesting paper, these results must be considered extremely preliminary, and need confirmation in other populations. Clearly this test is nowhere near ready for clinical use yet."

Further, he added, "The Alzheimer's Association does not agree that it is possible to prevent Alzheimer's disease. While a potential benefit of certain interventions, such as specific diets and NSAIDs, has been suggested, there is not nearly enough evidence to say they can prevent or delay the onset on the condition. These claims by the researchers have been overstated."

Tim Shakespeare, PhD, research officer at the UK Alzheimer's Society, had similar concerns. "If other researchers are able to replicate these results, it could possibly become a new diagnostic tool; however, because the study involved a very small number of people, it is far too soon to say whether this test will stand up to scrutiny," he said.

He noted that little previous research has assessed testing saliva as a diagnostic tool for Alzheimer's. "One previous study found much smaller differences in saliva levels of amyloid, but the measurements weren't accurate enough to be a useful diagnostic tool."

He reported that an Alzheimer's Society–funded study called PREVENT is looking at a range of markers, including blood, saliva, spinal fluid, and brain imaging, in a group of 700 people aged 40 to 59 years. Investigating how these markers develop over a period of 2 years will help to establish what the earliest signs of dementia are.

On interventions to prevent Alzheimer's, he said, "There are things people can do to reduce their risk, such as exercise and eating a healthy diet — however, it's important to note that people can develop Alzheimer's despite doing these things. Medium- or long-term use of NSAIDs may be associated with a reduced risk of developing Alzheimer's disease, but early drugs of this type can have severe side effects and it remains to be seen whether newer forms of these drugs could be effective."

The study was funded by Aurin Biotech. Dr McGeer is president and CEO of Aurin Biotech. Dr Knopman, Dr Fargo, and Dr Shakespeare have disclosed no relevant financial relationships.

J Alzheimers Dis. Published online October 24, 2016. Abstract

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