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Title: Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease
Author: Barranco Muñoz, Neus
Plá, Virginia
Alcolea, Daniel
Sánchez-Domínguez, Irene
Fischer-Colbrie, Reiner
Ferrer, Isidro
Lleó Bisa, Alberto
Aguado, Fernando
Keywords: Marcadors bioquímics
Malaltia d'Alzheimer
Biochemical markers
Alzheimer's disease
Issue Date: 26-Sep-2021
Publisher: Springer Science and Business Media LLC
Abstract: Background: 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. Methods: 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). Results: 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. Conclusions: 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.
Note: Reproducció del document publicat a:
It is part of: Translational Neurodegeneration, 2021, vol. 10, inum. 1
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ISSN: 2047-9158
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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