Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
Por:
Barranco, N, Pla, V, Alcolea, D, Sanchez-Dominguez, I, Fischer-Colbrie, R, Ferrer, I, Lleo, A, Aguado, F
Publicada:
26 sep 2021
Resumen:
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.
Filiaciones:
Barranco, N:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Barcelona 08028, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Pla, V:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Barcelona 08028, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Univ Rochester, Ctr Translat Neuromed, Med Ctr, Rochester, NY 14642 USA
Alcolea, D:
Autonomous Univ Barcelona, Dept Neurol, Memory Unit, St Pau Biomed Res Inst,St Pau Hosp, Barcelona 08041, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid 28031, Spain
Sanchez-Dominguez, I:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Barcelona 08028, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Fischer-Colbrie, R:
Innsbruck Med Univ, Dept Pharmacol, A-6020 Innsbruck, Austria
Ferrer, I:
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid 28031, Spain
Univ Barcelona, Dept Pathol & Expt Therapeut, Lhospitalet De Llobregat, Spain
Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Lhospitalet De Llobregat, Spain
Lleo, A:
Autonomous Univ Barcelona, Dept Neurol, Memory Unit, St Pau Biomed Res Inst,St Pau Hosp, Barcelona 08041, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid 28031, Spain
Aguado, F:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Barcelona 08028, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
gold, Green Published
|