A new skin test may eventually be used to diagnose Alzheimer's disease (AD), Parkinson's disease (PD), and other neurodegenerative diseases in living patients, new research shows.
Investigators at the Universidad Autonoma de San Luis Potosi and Hospital Central, San Luis Potosi, Mexico, found that skin biopsy specimens from patients with AD and those with PD had significantly higher levels of tau protein (p-Tau) compared with those from patients without these diseases and those from patients with nondegenerative dementias. In addition, patients with PD had higher levels of α-synuclein protein (α-Syn).
"There is now solid hope for a complementary test for the diagnosis of neurodegenerative diseases in living subjects, which can be done in a standard pathology lab in hospitals and clinical laboratories around the world," lead researcher Ildefonso Rodriguez-Leyva, MD, told Medscape Medical News.
Down the road, Dr Rodriguez-Leyva expects that neurologists will routinely order a skin test to formulate a differential diagnosis among several neurodegenerative diseases, including PD and AD.
The findings will be presented at the upcoming 67th American Academy of Neurology (AAN) Annual Meeting in April.
Thinking Outside the Brain
Although misfolded proteins reflect malfunctioning of the central nervous system in patients with AD and PD, protein alterations are also found outside the brain. For example, recent studies demonstrated that α-Syn can be detected in the gut, peripheral nerve terminals, and salivary glands.
"We hypothesised that the same proteins that undergo abnormal folding in the brain should present similar alterations in the skin," said Dr Rodriguez-Leyva.
For the study, investigators obtained a skim sample 4 mm in diameter from 65 participants: 20 with AD, 16 with PD, 17 with non-neurodegenerative dementia, and 12 apparently healthy and cognitively normal age-matched controls. Ages ranged from 62 to 85 years.
Dr Rodriguez-Leyva noted that the controls, who were selected from among the partners and caregivers of the patients, were also closely matched in terms of lifestyle, diet, socioeconomic status, and other factors.
After a series of steps to preserve the tissue, the researchers subjected the skin samples to immunohistochemistry, which, explained Dr Rodriguez-Leyva, consists of marking specific proteins contained in the tissue with molecules that recognize them.
"Once the protein in the tissue is recognized, a colored reaction indicates where and how many molecules of the tagged molecules are present in the tissue."
The researchers measured the reactivity against α-Syn and p-Tau antibodies.
The study found that compared with the healthy controls and patients with dementia caused by other conditions, those with both AD and PD had 7-fold higher levels of p-Tau. People with PD had an 8-fold higher level of α-Syn than the healthy controls.
Tau in PD
Although tau protein is a hallmark of AD, researchers have recently found tau deposits (neurofibrillary tangles) in the brains of patients with PD, said Dr Rodriguez-Leyva.
However, in PD, α-Syn is typically the protein that becomes altered, he said.
"The dying brain cells of patients present deposits of this protein combined with other cell debris called Lewy bodies, which provide the definitive diagnosis of Parkinson's disease when found through an autopsy," he noted.
For Dr Rodriguez-Leyva, the positive study results are gratifying because they support his hypothesis. In addition, they may have important implications for diagnosis, he said.
"These findings are relevant because, if they are corroborated by others, it could be a good option for diagnosing a neurodegenerative disease in living subjects," he said.
It's not yet possible to determine what amount of these proteins indicates the presence of disease, he said. "We need to test more patients at different points of disease progression in order to establish such a threshold level."
In addition, it's still too early to determine through this test the severity of the disease in a particular patient, he added.
Active Area of Research
Globally the amount of research focusing on molecular events underlying neurodegenerative diseases is increasing.
"Potential diagnostic methods are a very active research area around the world, due to the severity and the social and economic implications of these devastating diseases," said Dr Rodriguez-Leyva.
But while other researcher have looked for the relevant proteins in peripheral nervous system and other organs, "we are the only group working on a skin test," he said.
Looking to the future, Dr Rodriguez-Leyva said the skin biopsy may eventually become a standard test to help diagnose neurodegenerative diseases. He predicted that it's possible the test may detect not only AD and PD but also other neurodegenerative diseases, such as supranuclear progressive paralysis, frontotemporal dementia, and multiple sclerosis.
However, before that happens, other researchers must perform more studies to verify and replicate these results, he said.
For his part, Dr Rodriguez-Leyva is trying to secure resources to train technicians to perform the test in other parts of the country so the findings can be reproduced in larger samples.
Commenting on the findings for Medscape Medical News, Daniel O. Claassen, MD, assistant professor of neurology, Vanderbilt University, Nashville, Tennessee, said the study adds to the growing body of data showing that protein aggregates linked to neurodegeneration are often found outside the central nervous system.
"Why they are there, and how accessible they are for identification, is still not entirely clear," said Dr Claassen. "However, these findings have the potential to improve diagnostic accuracy. Larger multicenter replication studies are needed."
The study was supported by the National Council of Science and Technology of Mexico. Dr Rodriguez-Leyva has disclosed no relevant financial relationships.
To be presented at the 67th American Academy of Neurology (AAN) Annual Meeting, April 18-25, 2015.
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Cite this: Skin Test May Aid Alzheimer's, Parkinson's Diagnosis - Medscape - Feb 25, 2015.