Skin test pinpoints Alzheimer’s disease

A minimally invasive skin test can accurately diagnose Alzheimer’s disease (AD) with high sensitivity and specificity, even in the presence of comorbid conditions, according to new research.

Dr. Daniel Alcon

The test, which measures factors related to synaptic connections in the brain, could be added to other tests to “significantly improve the certainty of making [an AD] diagnostic,” said Daniel Alkon, MD, chief scientific advisor at SYNAPS Dx, the company behind the test. Medscape Medical News.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2022.

Better specificity required

Clinical trials testing potential therapies for Alzheimer’s disease typically include patients without a definitive diagnosis of Alzheimer’s disease-related dementia. Indeed, diagnoses are often uncertain, especially during the first 4 to 5 years of the disease.

Several tests for detecting AD signs have been developed. These include MRI and PET tests for amyloid plaque, cerebrospinal fluid and plasma measurements of soluble amyloid and tau, and blood levels of tau.

However, none of these tests were broadly validated at autopsy, Alkon said. Previous studies have shown that more than 50% of patients do not have AD alone. Instead, they also have other medical conditions, such as Parkinson’s disease, frontal lobe dementia or multi-infarct dementia, Alkon noted.

“It’s not enough for a test to discriminate Alzheimer’s disease from a control person who is not demented. It’s only useful if you can discriminate it from other types of dementia,” Alkon said.

He noted that while beta-amyloid and tau are used as “pathological red flags” to identify AD at autopsy, they are not effective in definitively diagnosing the disease because they are not closely correlated with cognitive deficits.

There is an “urgent unmet medical need” for a highly accurate and easily accessible AD biomarker, he said.

Enter the industry-certified DISCERN test (SYNAPS Dx) which measures factors related to synaptic connections in the brain, which Alkon says is a better indicator of AD than amyloid or tau. These factors include synaptic loss, neuronal death, inflammation, amyloid deposition, and tau protein hyperphosphorylation.

One of the tests in the test is the morphometric imaging test, which has previously been shown to closely correlate skin cell abnormalities with dementia and the presence of Alzheimer’s disease pathology in the brain. patients with Alzheimer’s disease.

“Studies correlate what’s happening in a patient’s brain with what’s happening elsewhere,” Alkon said. “Inference is [that] the disease has a systemic expression; it doesn’t just affect the brain, but the whole system.”

New and unique?

In the current study, researchers obtained a small sample of skin through a skin biopsy from 74 participants. Of these participants, 26 had Alzheimer’s disease, which was later confirmed following an autopsy; 21 had non-AD (non-ADD) dementia; and 27 did not have dementia and served as a control group.

The researchers found that the AD cell lines formed large aggregates, while the non-ADD or control group cell samples formed smaller and more numerous aggregates. The researchers then counted the number of aggregates and measured the average area of ​​the aggregates.

This led them to distinguish patients with AD from those without. The probability distributions of the morphometric imaging signals showed a clear separation of measurements for individual patients with AD and for group values ​​for patients without ADD.

Based on these results, the sensitivity of the MI test for the diagnosis of AD was determined to be 100% (95% CI, 86% – 100%), while the specificity was also 100% (CI 95%, 84% – 100%). .

The researchers also used samples from patients with dementia over the age of 55 who underwent a blinded autopsy examination. The specificity of AD was maintained even in cases of pathological comorbidity, including AD with dementias such as Parkinson’s disease, Pick’s disease and frontal lobe dementia.

“What’s new and unique is that we’ve shown that we can measure AD even in patients who have comorbidity, that is, patients who have these other dementias,” Alkon said.

Next steps

Alkon noted that this type of research takes time and requires “resources, perseverance and determination.” A death and confirmatory autopsy can occur years after a skin test and clinical diagnosis.

The company’s main lab is already testing samples from suspected AD cases, but “we’re preparing to roll out nationwide,” Alkon said.

“Clinicians should use all available arsenal measures before making a diagnosis of Alzheimer’s disease, and they should be thorough and cautious,” he added.

The company is currently seeking approval from the US Food and Drug Administration for the skin test and has received breakthrough status.

The test could help rule out other causes of dementia for which there are treatments, such as a thyroid disorder, major depression and vitamin B12 deficiency, Alkon noted.

He acknowledged that if the test indicates Alzheimer’s disease, there are few effective treatments available. “In my opinion, none of the drugs available today actually treat the underlying disease,” he said.

However, he noted that could change. Alkon is also president of Synaptogenix, a company developing therapeutics aimed at improving the synaptic growth pathway.

Early days

Commenting on the study of Medscape Medical NewsRebecca Edelmayer, PhD, senior director of science engagement at the Alzheimer’s Association, said she was encouraged by this skin prick test and other research into diagnosing Alzheimer’s disease.

However, she warned that these tests are at a very early stage. “An important step in advancing these tests for wider use is to study them in large-scale clinical trials,” Edelmayer said.

She noted that the DISCERN test analyzes protein kinase C (PKC) signaling markers, which have yet to be validated in large trials to support their use as a diagnosis of AD.

Edelmayer also pointed out that this test does not have FDA clearance. “It’s important that consumers are made aware of the extent or otherwise of the evaluation of these tools,” she said.

There is currently no single test that diagnoses AD, she added.

The study was funded by SYNAPS.

Alzheimer’s Association International Conference (AAIC) 2022: Abstract 63141. Presented July 31, 2022.

For more information about Medscape Neurology, join us on Facebook and Twitter