Neuropathology of Alzheimer's disease
Antonia Gutiérrez
PhD, Full Professor
Lab members
Jose Carlos Dávila, PhD
Elisabeth Sánchez Mejías, PhD
Laura Trujillo Estrada PhD
Juan Antonio García León, PhD
David Baglietto-Vargas PhD
Ines Moreno Gonzalez PhD
Marina Mejías Ortega PhD student
Laura Caceres Palomo PhD student
Lab contact
Institution
Our projects
The research of our group focuses on the pathogenesis of Alzheimer’s disease, and involves collaborations with several national and international labs working on different aspects of Alzheimer’s disease. Our efforts are aimed at understanding the role of glial (microglia and astrocytes) cells in the pathogenesis of Alzheimer’s disease, and at providing an integrative view of what happens in different cell populations during neurodegeneration. The group combines a wide range of cellular and molecular techniques, state-of-the-art microscopy methods and imaging tools, and behavioral studies in transgenic models of Alzheimer’s disease to better understand pathways causing glial dysfunction and neurodegeneration in Alzheimer’s disease. To address disease mechanisms of human relevance we make use of postmortem human specimens and human iPSC cells-derived cellular models. The long-term goal is to discover and validate novel glial-derived therapeutic targets that modify disease progression.
Specifically, we aim to:
-Understand glial responses in AD pathogenesis trying to connect glial dysfunction and neurodegeneration.
-Develop animal models of AD that recapitulate the glial pathology of patients, and perform preclinical studies with new therapeutic strategies.
-Generate glial cells from iPSCs to study novel pathogenic mechanisms and evaluate the efficacy of new drugs.
-Identify biomarkers and therapeutic targets that allow greater translational success to the human clinic.
Last publications
Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer’s mice and patients. Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC, Vitorica J, Gutierrez A. Brain Pathol. 30:345-363, 2020 doi: 10.1111/bpa.12785.
Use of human pluripotent stem cell-derived cells for neurodegenerative disease modeling and drug screening platform. Garcia-Leon JA, Vitorica J, Gutierrez A. Future Med Chem. 11:1305-1322, 2019 doi: 10.4155/fmc-2018-0520.
Amyloid-beta impairs TOM1-mediated IL-1R1 signaling. Martini AC, Gomez-Arboledas A, Forner S, Rodriguez-Ortiz CJ, McQuade A, Danhash E, Phan J, Javonillo D, Ha JV, Tram M, Trujillo-Estrada L, da Cunha C, Ager RR, Davila JC, Kitazawa M, Blurton-Jones M, Gutierrez A, Baglietto-Vargas D, Medeiros R, LaFerla FM. Proc Natl Acad Sci U S A. 2019 116:21198-21206, 2019 doi: 10.1073/pnas.1914088116.
Generation of oligodendrocytes and establishment of an all-human myelinating platform from human pluripotent stem cells. Garcia Leon JA, Garcia Diaz, B, Eggermont K, Caceres Palomo L, Neyrinck K, Madeiro Da Costa R, Davila JC, Anne Baron Van-Evercooren, Gutierrez A, and Verfaillie C. Nature Protocols 15, 3716–3744 (2020). doi.org/10.1038/s41596-020-0395-4
Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer’s disease. Sanchez-Mico MV, Jimenez S, Gomez-Arboledas A, Muñoz-Castro C, Romero-Molina C, Navarro V, Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Galea E, Davila JC, Vizuete M, Gutierrez A*, Vitorica J*. * corresponding authors Glia 2020, 1-15, doi: 10.1002/glia.23943
Enhancing microtubule stabilization rescue cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model. Fernandez-Valenzuela JJ, Sanchez-Varo R, Muñoz-Castro C, De Castro V, Sanchez-Mejias E, Navarro V, Jimenez S, Nuñez-Diaz C, Gomez-Arboledas A, Moreno-Gonzalez I, Vizuete M, Davila JC, Vitorica J and Gutierrez A. Scientific Reports 10(1):14776 (2020). doi: 10.1038/s41598-020-71767-4
Human Pluripotent Stem Cell-Derived Neural Cells as a Relevant Platform for Drug Screening in Alzheimer’s Disease. Garcia-Leon JA, Caceres-Palomo L, Sanchez-Mejias E, Mejias-Ortega M, Nuñez-Diaz C, Fernandez-Valenzuela JJ, Sanchez-Varo R, Davila JC, Vitorica J, Gutierrez A. Int J Mol Sci. 21(18): E6867 (2020). doi: 10.3390/ijms21186867
Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice. Larramona-Arcas R, González-Arias C, Perea G, Gutiérrez A, Vitorica J, García-Barrera T, Gómez-Ariza JL, Pascua-Maestro R, Ganfornina MD, Kara E, Hudry E, Martinez-Vicente M, Vila M, Galea E, Masgrau R. Mol Neurodegener 15(1):35 (2020). doi: 10.1186/s13024-020-00382-8.
Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease. Boza-Serrano A, Ruiz R, Sanchez-Varo R, García-Revilla J, Yang Y, Jimenez-Ferrer I, Paulus A, Wennström M, Vilalta A, Allendorf D, Davila JC, Stegmayr J, Jiménez S, Roca-Ceballos MA, Navarro-Garrido V, Swanberg M, Hsieh CL, Real LM, Englund E, Linse S, Leffler H, Nilsson UJ, Brown GC, Gutierrez A, Vitorica J, Venero JL, Deierborg T. Acta Neuropathol 138(2):251-273 (2019). doi: 10.1007/s00401-019-02013-z.
Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer’s disease. Gomez-Arboledas A, Davila JC, Sanchez-Mejias E, Navarro V, Nuñez-Diaz C, Sanchez-Varo R, Sanchez-Mico MV, Trujillo-Estrada L, Fernandez-Valenzuela JJ, Vizuete M, Comella JX, Galea E, Vitorica J, Gutierrez A. Glia. 66(3):637-653 (2018). doi: 10.1002/glia.23270.
Antonia Gutiérrez
PhD, Full Professor
Lab members
Jose Carlos Dávila, PhD
Elisabeth Sánchez Mejías, PhD
Laura Trujillo Estrada PhD
Juan Antonio García León, PhD
David Baglietto-Vargas PhD
Ines Moreno Gonzalez PhD
Marina Mejías Ortega PhD student
Laura Caceres Palomo PhD student
Lab contact
Institution
Our projects
The research of our group focuses on the pathogenesis of Alzheimer’s disease, and involves collaborations with several national and international labs working on different aspects of Alzheimer’s disease. Our efforts are aimed at understanding the role of glial (microglia and astrocytes) cells in the pathogenesis of Alzheimer’s disease, and at providing an integrative view of what happens in different cell populations during neurodegeneration. The group combines a wide range of cellular and molecular techniques, state-of-the-art microscopy methods and imaging tools, and behavioral studies in transgenic models of Alzheimer’s disease to better understand pathways causing glial dysfunction and neurodegeneration in Alzheimer’s disease. To address disease mechanisms of human relevance we make use of postmortem human specimens and human iPSC cells-derived cellular models. The long-term goal is to discover and validate novel glial-derived therapeutic targets that modify disease progression.
Specifically, we aim to:
-Understand glial responses in AD pathogenesis trying to connect glial dysfunction and neurodegeneration.
-Develop animal models of AD that recapitulate the glial pathology of patients, and perform preclinical studies with new therapeutic strategies.
-Generate glial cells from iPSCs to study novel pathogenic mechanisms and evaluate the efficacy of new drugs.
-Identify biomarkers and therapeutic targets that allow greater translational success to the human clinic.
Last publications
Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer’s mice and patients. Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC, Vitorica J, Gutierrez A. Brain Pathol. 30:345-363, 2020 doi: 10.1111/bpa.12785.
Use of human pluripotent stem cell-derived cells for neurodegenerative disease modeling and drug screening platform. Garcia-Leon JA, Vitorica J, Gutierrez A. Future Med Chem. 11:1305-1322, 2019 doi: 10.4155/fmc-2018-0520.
Amyloid-beta impairs TOM1-mediated IL-1R1 signaling. Martini AC, Gomez-Arboledas A, Forner S, Rodriguez-Ortiz CJ, McQuade A, Danhash E, Phan J, Javonillo D, Ha JV, Tram M, Trujillo-Estrada L, da Cunha C, Ager RR, Davila JC, Kitazawa M, Blurton-Jones M, Gutierrez A, Baglietto-Vargas D, Medeiros R, LaFerla FM. Proc Natl Acad Sci U S A. 2019 116:21198-21206, 2019 doi: 10.1073/pnas.1914088116.
Generation of oligodendrocytes and establishment of an all-human myelinating platform from human pluripotent stem cells. Garcia Leon JA, Garcia Diaz, B, Eggermont K, Caceres Palomo L, Neyrinck K, Madeiro Da Costa R, Davila JC, Anne Baron Van-Evercooren, Gutierrez A, and Verfaillie C. Nature Protocols 15, 3716–3744 (2020). doi.org/10.1038/s41596-020-0395-4
Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer’s disease. Sanchez-Mico MV, Jimenez S, Gomez-Arboledas A, Muñoz-Castro C, Romero-Molina C, Navarro V, Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Galea E, Davila JC, Vizuete M, Gutierrez A*, Vitorica J*. * corresponding authors Glia 2020, 1-15, doi: 10.1002/glia.23943
Enhancing microtubule stabilization rescue cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model. Fernandez-Valenzuela JJ, Sanchez-Varo R, Muñoz-Castro C, De Castro V, Sanchez-Mejias E, Navarro V, Jimenez S, Nuñez-Diaz C, Gomez-Arboledas A, Moreno-Gonzalez I, Vizuete M, Davila JC, Vitorica J and Gutierrez A. Scientific Reports 10(1):14776 (2020). doi: 10.1038/s41598-020-71767-4
Human Pluripotent Stem Cell-Derived Neural Cells as a Relevant Platform for Drug Screening in Alzheimer’s Disease. Garcia-Leon JA, Caceres-Palomo L, Sanchez-Mejias E, Mejias-Ortega M, Nuñez-Diaz C, Fernandez-Valenzuela JJ, Sanchez-Varo R, Davila JC, Vitorica J, Gutierrez A. Int J Mol Sci. 21(18): E6867 (2020). doi: 10.3390/ijms21186867
Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice. Larramona-Arcas R, González-Arias C, Perea G, Gutiérrez A, Vitorica J, García-Barrera T, Gómez-Ariza JL, Pascua-Maestro R, Ganfornina MD, Kara E, Hudry E, Martinez-Vicente M, Vila M, Galea E, Masgrau R. Mol Neurodegener 15(1):35 (2020). doi: 10.1186/s13024-020-00382-8.
Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease. Boza-Serrano A, Ruiz R, Sanchez-Varo R, García-Revilla J, Yang Y, Jimenez-Ferrer I, Paulus A, Wennström M, Vilalta A, Allendorf D, Davila JC, Stegmayr J, Jiménez S, Roca-Ceballos MA, Navarro-Garrido V, Swanberg M, Hsieh CL, Real LM, Englund E, Linse S, Leffler H, Nilsson UJ, Brown GC, Gutierrez A, Vitorica J, Venero JL, Deierborg T. Acta Neuropathol 138(2):251-273 (2019). doi: 10.1007/s00401-019-02013-z.
Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer’s disease. Gomez-Arboledas A, Davila JC, Sanchez-Mejias E, Navarro V, Nuñez-Diaz C, Sanchez-Varo R, Sanchez-Mico MV, Trujillo-Estrada L, Fernandez-Valenzuela JJ, Vizuete M, Comella JX, Galea E, Vitorica J, Gutierrez A. Glia. 66(3):637-653 (2018). doi: 10.1002/glia.23270.