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Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease.
Barranco, Neus; Plá, Virginia; Alcolea, Daniel; Sánchez-Domínguez, Irene; Fischer-Colbrie, Reiner; Ferrer, Isidro; Lleó, Alberto; Aguado, Fernando.
Afiliación
  • Barranco N; Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain.
  • Plá V; Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain.
  • Alcolea D; Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain.
  • Sánchez-Domínguez I; Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain.
  • Fischer-Colbrie R; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, 14642, USA.
  • Ferrer I; Memory Unit, Department of Neurology, Sant Pau Biomedical Research Institute. Sant Pau Hospital, Autonomous University of Barcelona, 08041, Barcelona, Spain.
  • Lleó A; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), 28031, Madrid, Spain.
  • Aguado F; Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain.
Transl Neurodegener ; 10(1): 37, 2021 09 26.
Article en En | MEDLINE | ID: mdl-34565482
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Disfunción Cognitiva Límite: Humans Idioma: En Revista: Transl Neurodegener Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Disfunción Cognitiva Límite: Humans Idioma: En Revista: Transl Neurodegener Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido