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1.
NPJ Parkinsons Dis ; 10(1): 116, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879633

RESUMEN

Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson's disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.

2.
Front Biosci (Landmark Ed) ; 28(10): 255, 2023 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-37919089

RESUMEN

The presence of protein aggregates is a hallmark of many neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been associated with the aggregation of specific proteins, which serve as disease-specific biomarkers. For example, aggregates of α-synuclein (α-syn) are found in α-synucleinopathies such as PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Similarly, AD is characterized by aggregates of amyloid-beta (Aß) and tau proteins. However, it has been observed that these protein aggregates can also occur in other neurodegenerative diseases, contributing to disease progression. For instance, α-syn aggregates have been detected in AD, Down syndrome, Huntington's disease, prion diseases, and various forms of FTLD. Similarly, Aß aggregates have been found in conditions like DLB and PD. Tau aggregates, in addition to being present in primary tauopathies, have been identified in prion diseases, α-synucleinopathies, and cognitively healthy aged subjects. Finally, aggregates of TDP-43, typically associated with FTLD and amyotrophic lateral sclerosis (ALS), have been observed in AD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), MSA, DLB, and other neurodegenerative diseases. These findings highlight the complexity of protein aggregation in neurodegeneration and suggest potential interactions and common mechanisms underlying different diseases. A deeper understating of this complex scenario may eventually lead to the identification of a better elucidation of the pathogenetic mechanisms of these devastating conditions and hopefully new therapeutic stragegies.


Asunto(s)
Enfermedad de Alzheimer , Degeneración Lobar Frontotemporal , Enfermedad por Cuerpos de Lewy , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Enfermedades por Prión , Sinucleinopatías , Humanos , Anciano , Enfermedades Neurodegenerativas/patología , Agregado de Proteínas , Enfermedad por Cuerpos de Lewy/metabolismo , Enfermedad por Cuerpos de Lewy/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Parkinson/metabolismo , Proteínas tau/metabolismo , Péptidos beta-Amiloides
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