Presence of Phosphorylated Tau, alpha-Synuclein and Amyloid Protein in the Skin of Patients with Clinical Diagnosis of Alzheimer Disease (S38.003)

OBJECTIVE The presence of misfolded proteins is the hallmark of neurodegeneration, and the specific biomarker can be identified in brain tissue. However, they are not exclusively found in the brain, but have systemic distribution, enabling the possibility to find them in several tissues. Our goal is to demonstrate their presence in the skin. POPULATION Eleven patients with clinical diagnosis of AD and image support, were studied with this procedure. METHODS Tau protein was evidenced by means of monoclonal antibodies recognizing two phosphorylation sites characteristic of AD (396 and 202, PHF (ab32057 ABCAM), and AT8, MN1020,Thermo Scientific, respectively). Also, antibodies against α-synuclein (α-syn, RB-9026-P, Thermo Scientific)) and β-amyloid (ab49455 ABCAM) were assayed. The immunohistochemical technique was performed in paraffin-embedded tissues and validated in parallel analysis of brain, peripheral nerve and skin tissue from autopsies. Biopsies from both, control (7) and diseased subjects (11) were processed and analyzed in a blind way. VALIDATION Brain sections of autopsies showed phosphorylated tau in cortical neurons of AD patients; positive α-synuclein (Lewy bodies) in mesencephalic neurons from a Parkinson disease patient, and amyloid plaques in AD brain. Scattered aggregates of phosphorylated tau protein were found in the epidermis, peripheral nerve terminals, dermis fibroblasts and skin appendages from patients with neurodegenerative diseases. RESULTS Cytoplasmic juxtanuclear positivity was observed in AD patients in epidermis and also in the cytoplasm of eccrine and sebaceous glands with PHF and AT8 antibodies. Significant difference (p = 0.007, Mann-Whitney U test) was observed between the positive immunostaining to AT8 antibody in the skin biopsy of control group and AD patients. Immunoreactivity to β-amyloid was also present in the dermis of AD patients. Antibody to α-synuclein stained the cytoplasm of melanocytes. CONCLUSION Aggregates of phosphorylated tau are present in the skin of AD patients and are non-detectable in control subjects. These findings require further confirmation, but have the potential of improving the diagnostic accuracy using a minimally invasive modality.