Parkinson disease and progressive supranuclear palsy: protein expression in skin

Ildefonso Rodríguez-Leyva, Erika G Chi-Ahumada, Juan Carrizales, Mayela Rodríguez-Violante, Salvador Velázquez-Osuna, Verónica Medina-Mier, María G Martel-Gallegos, Sergio Zarazúa, Lourdes Enríquez-Macías, Adriana Castro, Ana Laura Calderón-Garcidueñas, María E Jiménez-Capdeville, Ildefonso Rodríguez-Leyva, Erika G Chi-Ahumada, Juan Carrizales, Mayela Rodríguez-Violante, Salvador Velázquez-Osuna, Verónica Medina-Mier, María G Martel-Gallegos, Sergio Zarazúa, Lourdes Enríquez-Macías, Adriana Castro, Ana Laura Calderón-Garcidueñas, María E Jiménez-Capdeville

Abstract

Objective: This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP.

Material and methods: We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis.

Results: The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs.

Conclusion: These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

Figures

Figure 1
Figure 1
Identification of tau and α‐syn proteins. (A) Central nervous system. Neurofibrillary tangles in hippocampal neurons immunostained with PHF and AT8 antibodies in an AD patient (1000 and 400×), and Lewy body immunostained with α‐syn antibody in a mesencephalic neuron from a PD patient (1000×). Scale bar: 20 μm. (B) Immunoreactivity patterns of PHF, AT8, and α‐syn antibodies in peripheral nerve terminals. Scale bar: 10 μm. (C) Western blot. Demonstration of tau (PFH and AT8) and α‐syn (top) in RB, HB, and HS, Control: β‐actin (bottom). PHF, paired helical filaments; RB, rat brain; HB, human brain; HS, human skin.
Figure 2
Figure 2
Immunoreactivity patterns in epidermis. Control subject, PSP and PD patients with PFH, AT8, and α‐syn antibodies. Amine‐ethyl‐carbazole staining. Scale bar: 10 μm. PSP, progressive supranuclear paralysis; PD, Parkinson disease; PHF, paired helical filaments.
Figure 3
Figure 3
Skin immunofluorescence. Confocal microscopy. α‐syn (Cy5) and AT8 (Alexa Fluor 488) antibodies. Control subject (A–D), PSP patient (E–H) and PD patient (I–L). Cell nuclei stained with SYTOX. Scale bar 10 μm. PSP, progressive supranuclear paralysis; PD, Parkinson disease.
Figure 4
Figure 4
Immunopositivity quantification. PHF, AT8, and α‐syn immunopositivity expressed as percentage of immunopositive pixels/total area. PHF immunopositivity showed a similar pattern of expression in all groups (P = 0.72). AT8 immunoreactivity was significantly different in PSP and PD patients as compared with the control group (P < 0.001). α‐syn immunoreactivity in the PD group was significantly different from both control (P < 0.001) and PSP (P < 0.01) groups. Kruskal–Wallis analysis followed by Mann–Whitney U test. PHF, paired helical filaments; PSP, progressive supranuclear paralysis; PD, Parkinson disease.

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