Browsing by Subject "Tau"

Now showing 1 - 3 of 3
  • Repository logo
    Publication
    Restricted
    Age-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology
    (Elsevier, 2009-11-11) Van Groen, Thomas; Kadish, Inga; Caballero Bleda, María; Baño-Otalora, Beatriz; Vivanco, Pablo; Rol, María Ángeles; Madrid, Juan Antonio; Popovic, Natalija; Popovic Popovic, Miroljub; Anatomía Humana y Psicobiología
    Recently it has been shown that over 3-year-old wild-type South American rodents, Octodon degus, the "common degu" or degu, of their own accord develop Alzheimer's disease neuropathological hallmarks: amyloid-β-peptide depositions and accumulation of tau-protein. Here we analyzed brains of 1-, 3- and 6-year-old degu's, bred in standard animal facilities. Significant amounts of Aβ and tau deposits are present in the hippocampal formation of 6-year-old O. degus, primarily in the white matter, but these hippocampal Aβ and tau deposits are not present in younger ones. In contrast, significant Aβ deposits in blood vessel walls are already found in 3-year-old animals. The tau deposits in the hippocampal formation coincide with a significant decrease in staining for myelin in the same areas, indicating hippocampal disconnection and, likely, dysfunction. Our findings indicate that (1) cerebral amyloid angiopathy precedes brain parenchyma pathology in aged degu's and (2) the onset of disease seems to be delayed in the laboratory vs. wild-type degu's.
  • Thumbnail Image
    Publication
    Open Access
    Immune profiling of gliomas reveals a connection with IDH1/2 mutations, Tau function and the vascular phenotype
    (MDPI, 2020-11-02) Cejalvo, Teresa; Gargani, Ricardo; Segura Collar, Berta; Mata Martínez, Pablo; Herránz, Beatriz; Cantero, Diana; Ruano, Yoland; García Pérez, Daniel; Pérez Núñez, Ángel; Ramos, Ana; Hernández Laín, Aurelio; Martín Soberón, María Cruz; Sepúlveda Sánchez, Juan M.; Farmacología; Facultades de la UMU::Facultad de Medicina
    Background: Gliomas remain refractory to all attempted treatments, including those using immune checkpoint inhibitors. The characterization of the tumor (immune) microenvironment has been recognized as an important challenge to explain this lack of response and to improve the therapy of glial tumors. Methods: We designed a prospective analysis of the immune cells of gliomas by flow cytometry. Tumors with or without isocitrate dehydrogenase 1/2 (IDH1/2) mutations were included in the study. The genetic profile and the presence of different molecular and cellular features of the gliomas were analyzed in parallel. The findings were validated in syngeneic mouse models. Results: We observed that few immune cells infiltrate mutant IDH1/2 gliomas whereas the immune content of IDH1/2 wild-type tumors was more heterogeneous. Some of them contained an important immune infiltrate, particularly enriched in myeloid cells with immunosuppressive features, but others were more similar to mutant IDH1/2 gliomas, with few immune cells and a less immunosuppressive profile. Notably, we observed a direct correlation between the percentage of leukocytes and the presence of vascular alterations, which were associated with a reduced expression of Tau, a microtubule-binding protein that controls the formation of tumor vessels in gliomas. Furthermore, overexpression of Tau was able to reduce the immune content in orthotopic allografts of GL261 cells, delaying tumor growth. Conclusions: We have confirmed the reduced infiltration of immune cells in IDH1/2 mutant gliomas. By contrast, in IDH1/2 wild-type gliomas, we have found a direct correlation between the presence of vascular alterations and the entrance of leukocytes into the tumors. Interestingly, high levels of Tau inversely correlated with the vascular and the immune content of gliomas. Altogether, our results could be exploited for the design of more successful clinical trials with immunomodulatory molecules.
  • Thumbnail Image
    Publication
    Restricted
    Salivary biomarkers in Alzheimer’s disease
    (Springer, 2020-01-27) Tvarijonaviciute, Asta; Zamora, Carmen; Ceron, Jose; Bravo-Cantero, Antonio; Pardo-Marin, Luis; Valverde, Sandra; Lopez Jornet, Pia; Dermatología, Estomatología, Radiología y Medicina Física; Facultad de veterinaria Interlab UMU
    Objectives The objective of this study was to evaluate the changes that can occur in saliva components in patients with Alzheimer’s disease (AD) of different severity and determine if any of these components could be a biomarker of this disease. Therefore, a panel of selected analytes related to the amyloid cascade, the immune and adrenergic systems, among others, were analyzed in the saliva of patients with Alzheimer’s disease. Methods A total of 152 patients with AD and controls were included. The severity of the disease was established according to the Global Deterioration Scale. Unstimulated whole saliva was collected. Results Salivary amyloid-β42 was significantly lower, and complement C4 was significantly higher in the patients with AD than in the controls (p < 0.05 in both cases). Only complement C4 maintained its significant effect in the multivariate regression analysis. However, the area under the receiver operating characteristic curve of C4 was 0.613. No changes were found in any analyte regarding the severity of the disease. Conclusions A decrease in amyloid-β42 and an increase in complement C4 were detected in the saliva of patients with AD, but the changes did not show a high diagnostic performance for the detection of AD and were not associated with its severity. Clinical relevance Although some analytes showed significant differences in saliva in patients with AD, in our study conditions the salivary biomarkers analyzed were not of enough diagnostic utility for being used in routine