Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
| Autor: | Daniel Alcolea, Isidro Ferrer, Fernando Aguado, Reiner Fischer-Colbrie, Virginia Plá, Alberto Lleó, Irene Sánchez-Domínguez, Neus Barranco |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Cognitive Neuroscience Tau protein Cellular and Molecular Neuroscience Cerebrospinal fluid Alzheimer Disease Internal medicine medicine Humans Cognitive Dysfunction Granulovacuolar degeneration RC346-429 Cerebral Cortex biology business.industry Research Biochemical markers Neurodegeneration PCSK1 Alzheimer's disease Cerebral cortex PCSK2 medicine.disease Dense Core Vesicles Malaltia d'Alzheimer Endocrinology Secretory protein medicine.anatomical_structure Cystatin C Carboxypeptidase E Marcadors bioquímics biology.protein Biomarker (medicine) Neurology (clinical) Neurology. Diseases of the nervous system business Alzheimer’s disease Biomarkers |
| Zdroj: | Translational Neurodegeneration Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Translational Neurodegeneration, Vol 10, Iss 1, Pp 1-15 (2021) Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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