Initial skin test research shows promise but larger clinical studies needed before diagnostic tool could be ready for use by medical laboratories and pathologists
Researchers in Mexico developed a skin test that could lead to the early diagnosis of Alzheimer’s disease and pave the way for new therapies to treat a disease ranked as the sixth leading cause of death in the United States.
For clinical pathologists and medical laboratories, a testing breakthrough would be significant since the Alzheimer’s Association predicts that the number of Americans 65 and older with Alzheimer’s disease will reach 7.1 million by 2025, a 40% increase from today.
Researchers Were Looking for Unique Biomarkers
“Until now, pathological confirmation was not possible without a brain biopsy, so those diseases often go unrecognized until after the disease has progressed,” stated study author Ildefonso Rodriguez-Leyva, MD of Central Hospital at the University of San Luis Potosi, San Luis Potosi, Mexico, in an American Academy of Neurology (AAN) news release. “We hypothesized that since skin has the same origin as brain tissue while in the embryo that they might also show the same abnormal proteins. This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.”
Leyva’s research team took skin biopsies from behind the ears of study volunteers to look for the presence of two proteins:
• phosphorylated tau, and,
The study group included 20 Alzheimer’s patients, 16 Parkinson’s disease patients, and 17 patients with non-Alzheimer’s dementia. The researchers compared the study group’s biopsies to skin samples taken from 12 healthy people in the same age groups.
Biomarkers Could Be Used to Create Medical Laboratory Tests
The level of tau protein was found to be seven times higher in patients with both Alzheimer’s and Parkinson’s diseases. Alpha-synuclein protein also was found in Parkinson’s patients at eight times higher levels than in healthy patients from the control group.
Skin Biopsy Test May Be an Alternative to Costly Molecular Neuroimaging
The researchers published their study in the Feb. 25, 2015, issue of the Journal of Molecular Biomarkers & Diagnosis. They also presented their findings at the AAN’s annual meeting in April 2015.
“Biomarkers of neurodegenerative diseases have been developed in recent years, mainly based on advanced molecular neuroimaging,” they wrote in their published findings. “Most health systems in the world, however, cannot afford these studies for the clinical practice. Therefore, skin biopsies represent an alternative to support the diagnosis of the two most important neurodegenerative diseases, by applying immunohistochemistry with commercially available antibodies. This can be done in a standard pathology lab of worldwide hospitals and clinical laboratories.”
Because the results came from a small sample size of 65 people, Leyva told Scientific American that he wants to complete a larger study with the goal of producing a diagnostic skin test within two years.
“More research is needed to confirm these results, but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases. This also means tissue will be much more readily available for scientists to study. This procedure could be used to study not only Alzheimer’s and Parkinson’s, but also other neurodegenerative diseases,” Leyva stated in the AAN statement.
Experts Cautiously Optimistic
Some Alzheimer’s disease experts are taking a wait-and-see approach to this latest news, noting the many failed attempts to identify possible biomarkers of the disease. Today, a postmortem autopsy remains the only verifiable way to determine someone had Alzheimer’s.
Gandy is Associate Director of the Alzheimer’s Disease Research Center at Mount Sinai in New York City. He stated that he would “reserve judgment to see whether any totally independent group can reproduce the results.”
Scientific American also reported that Blanchette Rockefeller Neurosciences Institute is also planning larger clinical trials of their own skin test, which measures protein kinase C, epsilon (PKCE) levels as a means of diagnosing Alzheimer’s disease, in an attempt to replicate promising initial results.
Simon Ridley, MD, of Alzheimer’s Research UK told the BBC it was too early to say if a skin test would become available. He said research into biomarkers of cerebrospinal fluid was at a more advanced stage, but yet was not close to becoming a routine test.
Pathologists know that one aspect that would limit the value of a definitive medical laboratory test to diagnose Alzheimer’s is the lack of effective therapies for this disease. It is a well-known fact among clinical laboratory professionals that physicians are much slower to begin using a specific diagnostic test if there is not a useful therapy that can be implemented, based on the results of that lab test.
—Andrea Downing Peck