Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

Translational Neurodegeneration

Irene Sánchez-Domínguez¹  Neus Barranco¹  Virginia Plá¹  Fernando Aguado¹  Reiner Fischer-Colbrie²  Isidro Ferrer³  Alberto Lleó⁴  Daniel Alcolea⁴ 

[1] Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona;Department of Pharmacology, Innsbruck Medical University;Institute of Neurosciences, University of Barcelona;Memory Unit, Department of Neurology, Sant Pau Biomedical Research Institute. Sant Pau Hospital, Autonomous University of Barcelona;

关键词: Alzheimer’s disease;    Biomarkers;    Cerebral cortex;    Cerebrospinal fluid;    Granulovacuolar degeneration;    PCSK1;   

DOI  :  10.1186/s40035-021-00263-0

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown