Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
Barranco, Neus (Universitat de Barcelona. Institut de Neurociències)
Plá, Virginia (University of Rochester Medical Center)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Sánchez-Domínguez, Irene (Universitat de Barcelona)
Fischer-Colbrie, Reiner (Innsbruck Medical University)
Ferrer, Isidro (Institut d'Investigació Biomèdica de Bellvitge)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Aguado, Fernando (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD. The online version contains supplementary material available at 10. 1186/s40035-021-00263-0.
Grants:	Agencia Estatal de Investigación BFU2016-80868-R Agencia Estatal de Investigación PID2019-107738RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1255 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-0235 Instituto de Salud Carlos III PI18-00435 Instituto de Salud Carlos III PI14-1561 Instituto de Salud Carlos III PI17-01896
Note:	Altres ajuts: Generalitat de Catalunya PERIS SLT006/17/125
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; Biomarkers ; Cerebral cortex ; Cerebrospinal fluid ; Granulovacuolar degeneration ; PCSK1 ; PCSK2 ; Tau protein
Published in:	Translational Neurodegeneration, Vol. 10 (september 2021) , ISSN 2047-9158

DOI: 10.1186/s40035-021-00263-0
PMID: 34565482

15 p, 3.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles