Proteomics analysis of prefrontal cortex of Alzheimer’s disease patients revealed dysregulated proteins in the disease and novel proteins associated with amyloid-β pathology

Autor: Ana Montero-Calle, Raquel Coronel, María Garranzo-Asensio, Guillermo Solís-Fernández, Alberto Rábano, Vivian de los Ríos, María Jesús Fernández-Aceñero, Marta L. Mendes, Javier Martínez-Useros, Diego Megías, María Teresa Moreno-Casbas, Alberto Peláez-García, Isabel Liste, Rodrigo Barderas
Přispěvatelé: Instituto de Salud Carlos III, Ministerio de Educación, Cultura y Deporte (España), Research Foundation - Flanders, Montero-Calle, Ana, Coronel, Raquel, Garranzo Asensio, María, Solís-Fernández, Guillermo, Rábano, Alberto, de los Ríos, Vivian, Fernandez-Aceñero, M. Jesús, Mendes, Marta, Martínez-Useros, Javier, Moreno-Casbas, María Teresa, Peláez-García, Alberto, Liste, Isabel, Barderas, Rodrigo
Rok vydání: 2023
Předmět:
Zdroj: Cellular and Molecular Life Sciences. 80
ISSN: 1420-9071
1420-682X
DOI: 10.1007/s00018-023-04791-y
Popis: 26 p.-7 fig.-2 tab.
Background: Alzheimer’s disease (AD) is a progressive, chronic, and neurodegenerative disease, and the most common cause of dementia worldwide. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow getting further insights into the disease and identifying new markers for AD diagnosis.
Methods: aimed here to analyze protein dysregulation in AD brain by quantitative proteomics to identify novel proteins associated with the disease. 10-plex TMT (tandem mass tags)-based quantitative proteomics experiments were performed using frozen tissue samples from the left prefrontal cortex of AD patients and healthy individuals and vascular dementia (VD) and frontotemporal dementia (FTD) patients as controls (CT). LC–MS/MS analyses were performed using a Q Exactive mass spectrometer.
Results:In total, 3281 proteins were identified and quantified using MaxQuant. Among them, after statistical analysis with Perseus (p value
Conclusions: We identified and validated novel AD-associated proteins in brain tissue that should be of further interest for the study of the disease. Remarkably, PMP2 and SCRN3 were found to bind to amyloid-β (Aβ) fibers in vitro, and PMP2 to associate with Aβ plaques by IF, whereas HECTD1 and SLC12A5 were identified as new potential blood-based biomarkers of the disease.
This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B. The FPU predoctoral contract to A.M-C. is supported by the Spanish Ministerio de Educación, Cultura y Deporte. G.S-F. is recipient of a predoctoral contract (grant number 1193818N) supported by The Flanders Research Foundation (FWO). M. G-A. is recipient of a Margarita Salas postdoctoral grant for the requalification of the Spanish university system.
Databáze: OpenAIRE
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