| 2 | Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease显示文摘Background:New fuid biomarkers for Alzheimer’s disease(AD)that reveal synaptic and neural network dysfunc‑tions are needed for clinical practice and therapeutic trial design.Dense core vesicle(DCV)cargos are promising cerebrospinal fuid(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 astro‑cytes,whereas PC1/3,PC2 and CPE were also specifcally 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-specifc prohormone convertases in CSF and cortical tissues of AD patients.The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD. | Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez‑Domínguez Reiner Fischer‑Colbrie Isidro Ferrer Alberto Lleó Fernando Aguado | 2021 | Translational Neurodegeneration2021，10，3： | 0 |
| 3 | Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia显示文摘Background:Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases.Studies of glial fibrillary acidic protein(GFAP),an astrocytic damage marker,may help advance our understanding of different neurodegenerative diseases.In this study,we investigated the diagnostic performance of plasma GFAP(pGFAP),plasma neurofilament light chain(pNfL)and their combination for frontotemporal dementia(FTD)and Alzheimer's disease(AD)and their clinical utility in predicting disease progression.Methods:pGFAP and pNfL concentrations were measured in 72 FTD,56 AD and 83 cognitively normal(CN)participants using the Single Molecule Array technology.Of the 211 participants,199 underwent cerebrospinal(CSF)analysis and 122 had magnetic resonance imaging.We compared cross-sectional biomarker levels between groups,studied their diagnostic performance and assessed correlation between CSF biomarkers,cognitive performance and cortical thickness.The prognostic performance was investigated,analyzing cognitive decline through group comparisons by tertile.Results:Unlike pNfL,which was increased similarly in both clinical groups,pGFAP was increased in FTD but lower than in AD(all P<0.01).Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD(area under the curve[AUC]:combination 0.78;pGFAP 0.7;pNfL 0.61,all P<0.05).In FTD,pGFAP correlated with cognition,CSF and plasma NfL,and cortical thickness(all P<0.05).The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD(1.40 points annually,hazard ratio[HR]3.82,P<0.005)and in AD(1.20 points annually,HR 2.26,P<0.005).Conclusions:pGFAP and pNfL levels differ in FTD and AD;and their combination is useful for distinguishing between the two diseases.pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD. | Nuole Zhu Miguel Santos-Santos Ignacio lllán-Gala Victor Montal Teresa Estellés Isabel Barroeta Miren Altuna Javier Arranz Laia Muñoz Olivia Belbin Isabel Sala Maria Belén Sánchez-Saudinós Andrea Subirana Laura Videla Jordi Pegueroles Rafael Blesa Jordi Clarimón Maria Carmona-Iragui Juan Fortea Alberto Lleó Daniel Alcolea | 2021 | Translational Neurodegeneration2021，10，4： | 0 |
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