Skin biopsies can be used to detect elevated levels of abnormal proteins associated with Alzheimer’s and Parkinson’s diseases (AD and PD), according to two studies presented at the American Academy of Neurology’s annual meeting (Washington, D.C.; April 1825). The researchers showed that phosphorylated Tau (p-Tau) and α-synuclein (α-Syn) are present in the skin from patients with the conditions and that the protein levels can be quantified using image analysis techniques. The current gold standard for the definitive diagnosis of neurodegenerative diseases is the demonstration of misfolded proteins in postmortem brain samples. Diagnosis in living patients is primarily based on clinical observations, but biomarkers of Alzheimer’s and Parkinson’s have long been sought. “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,” said study author Ildefonso Rodriguez-Leyva, M.D., from University of San Luis Potosi (Mexico), in a statement. “This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.” The researchers presented findings from two related studies. First, they evaluated skin biopsies from behind the ear in 65 individuals (20 with AD, 16 with PD, 17 with non-neurodegenerative […]
Skin biopsies can be used to detect elevated levels of abnormal proteins associated with Alzheimer’s and Parkinson’s diseases (AD and PD), according to two studies presented at the American Academy of Neurology’s annual meeting (Washington, D.C.; April 1825). The researchers showed that phosphorylated Tau (p-Tau) and α-synuclein (α-Syn) are present in the skin from patients with the conditions and that the protein levels can be quantified using image analysis techniques.
The current gold standard for the definitive diagnosis of neurodegenerative diseases is the demonstration of misfolded proteins in postmortem brain samples. Diagnosis in living patients is primarily based on clinical observations, but biomarkers of Alzheimer’s and Parkinson’s have long been sought.
“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,” said study author Ildefonso Rodriguez-Leyva, M.D., from University of San Luis Potosi (Mexico), in a statement. “This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.”
The researchers presented findings from two related studies. First, they evaluated skin biopsies from behind the ear in 65 individuals (20 with AD, 16 with PD, 17 with non-neurodegenerative dementia, and 12 age-matched healthy controls). They measured the reactivity against antibodies for p-Tau and α-Syn both in sections of paraffin embedded tissue and in proteins extracted from tissue homogenates. Light and confocal microscopy identified protein aggregates by immunohistochemistry and their presence in the skin was confirmed through Western blots. Immuno-positivity was characterized by: percentage of positive cells, a semi-quantitative scale, and through image analysis software. The skin biopsies from AD and PD patients had significantly higher levels of p-Tau immunopositivity, compared both to controls and patients with non-degenerative dementia. Those with AD and PD had seven times higher levels of p-Tau protein. People with Parkinson’s had an eight times higher level of α-Syn protein than the healthy control group.
In the second abstract, the researchers demonstrated quantification of the expression of p-Tau protein in skin cells by selective correction processing and image colorimetric analysis. Tau inmunopositivity obtained in pixels by selective correction in Adobe Photoshop and colorimetry in IPP were compared with the quantification estimated by manual counting of immunopositive cells assisted by a computer. Image colorimetric quantification of the immunopositive area, the authors say, allows for a more objective comparison.
Rodriguez-Leyva tells DTET that the test can be performed in a standard pathology laboratory with an immunohistochemistry area, but cautions that independent validation in broader ethnic samples of patients is necessary to prove the utility of the test. Clinical use of such a test could be five years away, he estimates.
Takeaway: With independent validation, the findings could represent a breakthrough in the ability to definitively diagnose AD and PD in living patients.
