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Author Raquel Sanchez Varo

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Animal and Cellular Models of Alzheimer's Disease: Progress, Promise, and Future Approaches.

Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nuñez-Diaz, Jose Carlos Davila, Javier Vitorica, Frank M LaFerla, Ines Moreno-Gonzalez, Antonia Gutierrez, David Baglietto-Vargas,

Alzheimer's disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease ... Read more >>

Neuroscientist (The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry)
[2021, :10738584211001753]

Cited: 0 times

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Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease.

Maria V Sanchez-Mico, Sebastian Jimenez, Angela Gomez-Arboledas, Clara Muñoz-Castro, Carmen Romero-Molina, Victoria Navarro, Elisabeth Sanchez-Mejias, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Elena Galea, José C Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid-β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced ... Read more >>

Glia (Glia)
[2021, 69(4):997-1011]

Cited: 2 times

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Human Pluripotent Stem Cell-Derived Neural Cells as a Relevant Platform for Drug Screening in Alzheimer's Disease.

Juan Antonio Garcia-Leon, Laura Caceres-Palomo, Elisabeth Sanchez-Mejias, Marina Mejias-Ortega, Cristina Nuñez-Diaz, Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez,

Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tangles are prime features of Alzheimer's disease (AD). The pathology of AD is very complex and still not fully understood, since different neural cell types are involved in the disease. Although neuronal function is clearly deteriorated in AD patients, recently, an increasing number ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2020, 21(18):]

Cited: 4 times

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Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model.

Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Clara Muñoz-Castro, Vanessa De Castro, Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Cristina Nuñez-Diaz, Angela Gomez-Arboledas, Ines Moreno-Gonzalez, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez,

In Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):14776]

Cited: 0 times

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Editorial: Risk Factors for Alzheimer's Disease.

Ines Moreno-Gonzalez, Rodrigo Morales, David Baglietto-Vargas, Raquel Sanchez-Varo,

Front Aging Neurosci (Frontiers in aging neuroscience)
[2020, 12:124]

Cited: 1 time

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Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer's disease.

Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Juan García-Revilla, Yiyi Yang, Itzia Jimenez-Ferrer, Agnes Paulus, Malin Wennström, Anna Vilalta, David Allendorf, Jose Carlos Davila, John Stegmayr, Sebastian Jiménez, Maria A Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine L Hsieh, Luis M Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf J Nilsson, Guy C Brown, Antonia Gutierrez, Javier Vitorica, Jose Luis Venero, Tomas Deierborg,

Alzheimer's disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2019, 138(2):251-273]

Cited: 32 times

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Galectin-3, A Novel Endogenous Trem2 Ligand, Regulates Inflammatory Response and Aβ Fibrilation in Alzheimer’s Disease

Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Yiyi Yang, Juan García-Revilla, Itzia Jimenez-Ferrer, Agnes Paulus, Malin Wennström, Anna Vilalta, David Allendorf, Jose Carlos Davila, Christopher Dunning, John Stegmayr, Sebastian Jiménez, Maria Angustias Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine Hsieh, Luis Miguel-Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf Nilsson, Antonia Gutierrez, Guy Brown, Javier Vitorica, Jose Luis Venero, Tomas Deierborg, ,

<h4>ABSTRACT</h4> Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, intraneuronal tau neurofibrillary tangles and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the ... Read more >>

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Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology.

Carmen Romero-Molina, Victoria Navarro, Raquel Sanchez-Varo, Sebastian Jimenez, Juan J Fernandez-Valenzuela, Maria V Sanchez-Mico, Clara Muñoz-Castro, Antonia Gutierrez, Javier Vitorica, Marisa Vizuete,

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau ... Read more >>

Front Cell Neurosci (Frontiers in cellular neuroscience)
[2018, 12:421]

Cited: 5 times

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Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease.

Angela Gomez-Arboledas, Jose C Davila, Elisabeth Sanchez-Mejias, Victoria Navarro, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Juan Jose Fernandez-Valenzuela, Marisa Vizuete, Joan X Comella, Elena Galea, Javier Vitorica, Antonia Gutierrez,

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this ... Read more >>

Glia (Glia)
[2018, 66(3):637-653]

Cited: 46 times

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Microglia in Alzheimer's Disease: Activated, Dysfunctional or Degenerative.

Victoria Navarro, Elisabeth Sanchez-Mejias, Sebastian Jimenez, Clara Muñoz-Castro, Raquel Sanchez-Varo, Jose C Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, ... Read more >>

Front Aging Neurosci (Frontiers in aging neuroscience)
[2018, 10:140]

Cited: 37 times

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Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer's disease.

David Baglietto-Vargas, Elisabeth Sánchez-Mejias, Victoria Navarro, Sebastián Jimenez, Laura Trujillo-Estrada, Angela Gómez-Arboledas, Maria Sánchez-Mico, Raquel Sánchez-Varo, Marisa Vizuete, José Carlos Dávila, José Manuel García-Verdugo, Javier Vitorica, Antonia Gutierrez,

Alzheimer's disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer's patients. In this regard, new evidence linking Alzheimer's disease-related pathology and neuronal stem cells ... Read more >>

Sci Rep (Scientific reports)
[2017, 7(1):10085]

Cited: 11 times

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Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity.

Ana Peñalver, José A Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, Mercedes Martín-Rufián, Guillermo Estivill-Torrús, Raquel Sánchez-Varo, Francisco J Alonso, Mercedes Pérez-Hernández, María I Colado, Antonia Gutiérrez, Fernando Rodríguez de Fonseca, Javier Márquez,

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA<sub>1</sub> receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA<sub>1</sub> mice. ... Read more >>

Front Mol Neurosci (Frontiers in molecular neuroscience)
[2017, 10:278]

Cited: 6 times

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Soluble phospho-tau from Alzheimer's disease hippocampus drives microglial degeneration.

Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Maria Sanchez-Mico, Raquel Sanchez-Varo, Cristina Nuñez-Diaz, Laura Trujillo-Estrada, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

The role of microglial cells in the development and progression of Alzheimer's disease (AD) has not been elucidated. Here, we demonstrated the existence of a weak microglial response in human AD hippocampus which is in contrast to the massive microglial activation observed in APP-based models. Most importantly, microglial cells displayed ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2016, 132(6):897-916]

Cited: 47 times

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In vivo modification of Abeta plaque toxicity as a novel neuroprotective lithium-mediated therapy for Alzheimer's disease pathology.

Laura Trujillo-Estrada, Sebastian Jimenez, Vanessa De Castro, Manuel Torres, David Baglietto-Vargas, Ines Moreno-Gonzalez, Victoria Navarro, Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

<h4>Background</h4>Alzheimer's disease (AD) is characterized by the abnormal accumulation of extracellular beta-amyloid (Abeta) plaques, intracellular hyperphosphorylated tau, progressive synaptic alterations, axonal dystrophies, neuronal loss and the deterioration of cognitive capabilities of patients. However, no effective disease-modifying treatment has been yet developed. In this work we have evaluated whether chronic lithium ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2013, 1:73]

Cited: 12 times

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Early neuronal loss and axonal/presynaptic damage is associated with accelerated amyloid-β accumulation in AβPP/PS1 Alzheimer's disease mice subiculum.

Laura Trujillo-Estrada, José Carlos Dávila, Elisabeth Sánchez-Mejias, Raquel Sánchez-Varo, Angela Gomez-Arboledas, Marisa Vizuete, Javier Vitorica, Antonia Gutiérrez,

The progressive cognitive decline leading to dementia in Alzheimer's disease (AD) patients is the consequence of a severe loss of synapses and neurons affecting particular cell subpopulations in selected brain areas, with the subiculum being one of the earliest regions displaying severe atrophy and pathology. The lack of significant neuronal ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2014, 42(2):521-541]

Cited: 20 times

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Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

Manuel Torres, Sebastian Jimenez, Raquel Sanchez-Varo, Victoria Navarro, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Irene Carmona, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

<h4>Background</h4>Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that ... Read more >>

Mol Neurodegener (Molecular neurodegeneration)
[2012, 7:59]

Cited: 52 times

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Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer's mice hippocampus.

Raquel Sanchez-Varo, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Manuel Torres, David Baglietto-Vargas, Ines Moreno-Gonzalez, Vanessa De Castro, Sebastian Jimenez, Diego Ruano, Marisa Vizuete, Jose Carlos Davila, Jose Manuel Garcia-Verdugo, Antonio Jesus Jimenez, Javier Vitorica, Antonia Gutierrez,

Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer's disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1(M146L)/APP(751SL) mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2012, 123(1):53-70]

Cited: 94 times

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Age-dependent accumulation of soluble amyloid beta (Abeta) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-alpha (sAPP(alpha)) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3beta pathway in Alzheimer mouse model.

Sebastian Jimenez, Manuel Torres, Marisa Vizuete, Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Irene Carmona-Cuenca, Cristina Caballero, Diego Ruano, Antonia Gutierrez, Javier Vitorica,

Neurotrophins, activating the PI3K/Akt signaling pathway, control neuronal survival and plasticity. Alterations in NGF, BDNF, IGF-1, or insulin signaling are implicated in the pathogenesis of Alzheimer disease. We have previously characterized a bigenic PS1×APP transgenic mouse displaying early hippocampal Aβ deposition (3 to 4 months) but late (17 to 18 ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2011, 286(21):18414-18425]

Cited: 96 times

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Calretinin interneurons are early targets of extracellular amyloid-beta pathology in PS1/AbetaPP Alzheimer mice hippocampus.

David Baglietto-Vargas, Ines Moreno-Gonzalez, Raquel Sanchez-Varo, Sebastian Jimenez, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Manuel Torres, Manuel Romero-Acebal, Diego Ruano, Marisa Vizuete, Javier Vitorica, Antonia Gutierrez,

Specific neuronal networks are preferentially affected in the early stages of Alzheimer's disease (AD). The distinct subpopulations of hippocampal inhibitory GABAergic system have been shown to display differential vulnerability to neurodegeneration in AD. We have previously reported a substantial loss of SOM/NPY interneurons, whereas those expressing parvalbumin were unaltered, in ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2010, 21(1):119-132]

Cited: 51 times

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Extracellular amyloid-beta and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1(M146L)/APP(751SL) mice.

Ines Moreno-Gonzalez, David Baglietto-Vargas, Raquel Sanchez-Varo, Sebastian Jimenez, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Juan Carlos Del Rio, Manuel Torres, Manuel Romero-Acebal, Diego Ruano, Marisa Vizuete, Javier Vitorica, Antonia Gutierrez,

Here we demonstrated that extracellular, not intracellular, amyloid-beta (Abeta) and the associated cytotoxic glial neuroinflammatory response are major contributors to early neuronal loss in a PS1xAPP model. A significant loss of principal (27%) and SOM/NPY (56-46%) neurons was found in the entorhinal cortex at 6 months of age. Loss of ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2009, 18(4):755-776]

Cited: 20 times

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Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: age-dependent switch in the microglial phenotype from alternative to classic.

Sebastian Jimenez, David Baglietto-Vargas, Cristina Caballero, Ines Moreno-Gonzalez, Manuel Torres, Raquel Sanchez-Varo, Diego Ruano, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Although the microglial activation is concomitant to the Alzheimer's disease, its precise role (neuroprotection vs neurodegeneration) has not yet been resolved. Here, we show the existence of an age-dependent phenotypic change of microglial activation in the hippocampus of PS1xAPP model, from an alternative activation state with Abeta phagocytic capabilities (at ... Read more >>

J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience)
[2008, 28(45):11650-11661]

Cited: 198 times

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Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons.

M Paz Gavilán, Elisa Revilla, Cristina Pintado, Angélica Castaño, M Luisa Vizuete, Inés Moreno-González, David Baglietto-Vargas, Raquel Sánchez-Varo, Javier Vitorica, Antonia Gutiérrez, Diego Ruano,

Increased neuroinflammatory reaction is frequently observed during normal brain aging. However, a direct link between neuroinflammation and neurodegeneration during aging has not yet been clearly shown. Here, we have characterized the age-related hippocampal inflammatory processes and the potential relation with hippocampal neurodegeneration. The mRNA expression of the pro-inflammatory cytokines IL-1beta ... Read more >>

J Neurochem (Journal of neurochemistry)
[2007, 103(3):984-996]

Cited: 45 times

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Inter-individual variability in the expression of the mutated form of hPS1M146L determined the production of Abeta peptides in the PS1xAPP transgenic mice.

Cristina Caballero, Sebastian Jimenez, Ines Moreno-Gonzalez, David Baglietto-Vargas, Raquel Sanchez-Varo, M Paz Gavilan, Blanca Ramos, Juan Carlos Del Rio, Marisa Vizuete, Antonia Gutierrez, Diego Ruano, Javier Vitorica,

The detection of the early phenotypic modifications of Alzheimer's disease (AD) models is fundamental to understand the progression and identify pharmacologic targets of this pathology. However, a large variability within different models and between age-matched mice from the same model has been observed. This variability could be due to heterogeneity ... Read more >>

J Neurosci Res (Journal of neuroscience research)
[2007, 85(4):787-797]

Cited: 6 times

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