Procedencia: Facultad de medicina - UASLP


The presence of misfolded proteins in the brain is the hallmark of neurodegenerative diseases, which are nowadays considered systemic proteinopathies. The clinical differentiation between the main neurodegenerative diseases depends on the protein that becomes misfolded, the initiation, propagation and final distribution of its aggregation and inclusion bodies. Alzheimer disease (AD) comprises Tau and β-amyloid proteinopathies, while Parkinson disease (PD) is defined as a synucleinopathy, although there is considerable overlap of misfolded proteins among neurodegeneratives diseases. Those proteins could have systemic expression and might be found in several tissues including the skin. Light and confocal microscopy were employed to demonstrate by immunohistochemistry the presence of phosphorylated Tau (p-Tau) and of α-Synuclein (ASyn) in skin biopsies of patients with AD and PD. The presence of the proteins was confirmed through Western blots. Antibodies against p-Tau (PHF, phosphorylated at S296 and AT8, phosphorylated at S202) and ASyn were assayed in biopsied tissue from the retro-auricular area in patients with AD and PD. These antibodies were first tested in autopsied brain tissue from confirmed AD and PD cases. Both anti-tau antibodies reacted positively with cortical and hippocampal neurofibrillary tangles and the anti-ASyn antibody with Lewy bodies in the mesencephalon.  AD patients were compared with healthy subjects and patients with non-degenerative dementia (NND). PD patients were also compared with healthy subjects and with progressive supranuclear palsy (PSP) patients, who present a parkinsonism that is clinically difficult to distinguish from PD. In the skin, PHF immunopositivity was present along the different cell types conforming the epidermis, dermis, pilosebaceous unit, eccrine glands and in all peripheral nerve terminals, both in healthy individuals and in all groups of patients. By contrast, healthy subjects and NDD patients showed minimal staining using AT8 and α-syn antibodies. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the AD and PSP groups only expressed higher AT8 immunopositivity than healthy controls and NDD patients. Ongoing studies using qPCR confirm the expression of mRNA of Tau in epidermis cells as well as in oral mucosa cells. In conclusion, skin biopsies could support the clinical diagnosis of neurodegenerative diseases.