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PreprintCited by 176Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Astrocytes in Alzheimer´s Disease: Pathological Significance and Molecular Pathways

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Preman, Pranav, Alfonso-Triguero, Maria, Alberdi, Elena, Verkhratsky, Alexej, Arranz, Amaia M·2021·Cells
DOI 10.20944/preprints202102.0230.v1PMC PMC7999452

Preprint — published as 10.3390/cells10030540 · Paper page

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Abstract

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

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  1. Chvátal, A.; Verkhratsky, A. An Early History of Neuroglial Research: Personalities. Neuroglia 2018, 1, 245-281. [CrossRef] · DOI
  2. Ramón y Cajal, S. Contribución Al Conocimiento de La Neuroglia Del Cerebro Humano. Trab. Lab. Invest. Biol. Univ. Madr. 1913, 11, 255-315.
  3. Molofsky, A.V.; Deneen, B. Astrocyte development: A Guide for the Perplexed. Glia 2015, 63, 1320-1329. [CrossRef] · DOI
  4. Schitine, C.; Nogaroli, L.; Costa, M.R.; Hedin-Pereira, C. Astrocyte Heterogeneity in the Brain: From Development to Disease. Front. Cell. Neurosci. 2015, 9. [CrossRef] · DOI
  5. Verkhratsky, A.; Nedergaard, M. Physiology of Astroglia. Physiol. Rev. 2018, 98, 239-389. [CrossRef] · DOI · Paper page
  6. Guillemot, F. Cell fate specification in the mammalian telencephalon. Prog. Neurobiol. 2007, 83, 37-52. [CrossRef] · DOI
  7. He, F.; Ge, W.; Martinowich, K.; Becker-Catania, S.; Coskun, V.; Zhu, W.; Wu, H.; Castro, D.; Guillemot, F.; Fan, G.; et al. A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat. Neurosci. 2005, 8, 616-625. [CrossRef] [PubMed] · DOI
  8. Nakashima, K.; Yanagisawa, M.; Arakawa, H.; Taga, T. Astrocyte differentiation mediated by LIF in cooperation with BMP2. FEBS Lett. 1999, 457, 43-46. [CrossRef] · DOI
  9. Freeman, M.R. Specification and Morphogenesis of Astrocytes. Science 2010, 330, 774-778. [CrossRef] [PubMed] · DOI
  10. Kanski, R.; Van Strien, M.E.; Van Tijn, P.; Hol, E.M. A star is born: New insights into the mechanism of astrogenesis. Cell. Mol. Life Sci. 2013, 71, 433-447. [CrossRef] · DOI
  11. Urayama, S.; Semi, K.; Sanosaka, T.; Hori, Y.; Namihira, M.; Kohyama, J.; Takizawa, T.; Nakashima, K. Chromatin Accessibility at a STAT3 Target Site Is Altered Prior to Astrocyte Dif-ferentiation. Cell Struct. Funct. 2013, 38, 55-66. [CrossRef] [PubMed] · DOI
  12. Gross, R.E.; Mehler, M.F.; Mabie, P.C.; Zang, Z.; Santschi, L.; Kessler, J.A. Bone Morphogenetic Proteins Promote Astroglial Lineage Commitment by Mammalian Subventricular Zone Progenitor Cells. Neuron 1996, 17, 595-606. [CrossRef] · DOI
  13. Krencik, R.; van Asperen, J.V.; Ullian, E.M. Human astrocytes are distinct contributors to the complexity of synaptic function. Brain Res. Bull. 2017, 129, 66-73. [CrossRef] [PubMed] · DOI
  14. Qin, S.; Niu, W.; Iqbal, N.; Smith, D.K.; Zhang, C.L. Orphan Nuclear Receptor TLX Regulates Astrogenesis by Modulating BMP Signaling. Front. Neurosci. 2014, 8, 74. [CrossRef] · DOI
  15. Takizawa, T.; Ochiai, W.; Nakashima, K.; Taga, T. Enhanced gene activation by Notch and BMP signaling cross-talk. Nucleic Acids Res. 2003, 31, 5723-5731. [CrossRef] · DOI
  16. Ge, W.P.; Miyawaki, A.; Gage, F.H.; Jan, Y.N.; Jan, L.Y. Local Generation of Glia Is a Major Astrocyte Source in Postnatal Cortex. Nature 2012, 484, 376-380. [CrossRef] [PubMed] · DOI · Paper page
  17. Dimou, L.; Simon, C.; Kirchhoff, F.; Takebayashi, H.; Götz, M. Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex. J. Neurosci. 2008, 28, 10434-10442. [CrossRef] · DOI · Paper page
  18. Du, X.; Zhang, Z.; Zhou, H.; Zhou, J. Differential Modulators of NG2-Glia Differentiation into Neurons and Glia and Their Crosstalk. Cell. Mol. Neurobiol. 2021, 41, 1-15. [CrossRef] · DOI
  19. Huang, W.; Guo, Q.; Bai, X.; Scheller, A.; Kirchhoff, F. Early Embryonic NG2 Glia Are Ex-clusively Gliogenic and Do Not Generate Neurons in the Brain. GLIA 2019, 67, 1094-1103. [CrossRef] · DOI
  20. Gomes, W.A.; Mehler, M.F.; Kessler, J.A. Transgenic Overexpression of BMP4 Increases Astroglial and Decreases Oligodendroglial Lineage Commitment. Dev. Biol. 2003, 255, 164-177. [CrossRef] · DOI
  21. Von Bartheld, C.S.; Bahney, J.; Herculano-Houzel, S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J. Comp. Neurol. 2016, 524, 3865-3895. [CrossRef] · DOI · Paper page
  22. Sherwood, C.C.; Stimpson, C.D.; Raghanti, M.A.; Wildman, D.E.; Uddin, M.; Grossman, L.I.; Goodman, M.; Redmond, J.C.; Bonar, C.J.; Erwin, J.M.; et al. Evolution of In-creased Glia-Neuron Ratios in the Human Frontal Cortex. Proc. Natl. Acad. Sci. USA 2006, 103, 13606-13611. [CrossRef] [PubMed] · DOI · Paper page
  23. Azevedo, F.A.; Carvalho, L.R.; Grinberg, L.T.; Farfel, J.M.; Ferretti, R.E.; Leite, R.E.; Jacob Filho, W.J.; Lent, R.; Herculano-Houzel, S. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol 2009, 513, 532-541. [CrossRef] [PubMed] · DOI · Paper page
  24. Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.; Pakkenberg, B. Neocortical Glial Cell Numbers in Human Brains. Neurobiol. Aging 2008, 29, 1754-1762. [CrossRef] · DOI · Paper page
  25. Keller, D.; Erö, C.; Markram, H. Cell Densities in the Mouse Brain: A Systematic Review. Front. Neuroanat. 2018, 12, 83. [CrossRef] · DOI · Paper page
  26. Verkhratsky, A. Physiology of neuronal-glial networking. Neurochem. Int. 2010, 57, 332-343. [CrossRef] · DOI
  27. Rose, C.R.; Verkhratsky, A. Principles of sodium homeostasis and sodium signalling in astroglia. Glia 2016, 64, 1611-1627. [CrossRef] · DOI
  28. Verkhratsky, A.; Rose, C.R. Na+-dependent transporters: The backbone of astroglial homeostatic function. Cell Calcium 2020, 85, 102136. [CrossRef] [PubMed] · DOI
  29. Verkhratsky, A.; Semyanov, A.; Zorec, R. Physiology of Astroglial Excitability. Function 2020, 1, 16. [CrossRef] · DOI
  30. Vasile, F.; Dossi, E.; Rouach, N. Human astrocytes: Structure and functions in the healthy brain. Anat. Embryol. 2017, 222, 2017-2029. [CrossRef] [PubMed] · DOI · Paper page
  31. Verkhratsky, A.; Nedergaard, M. Astroglial cradle in the life of the synapse. Philos. Trans. R. Soc. B Biol. Sci. 2014, 369, 20130595. [CrossRef] · DOI · Paper page
  32. Allen, N.J.; Eroglu, C. Cell Biology of Astrocyte-Synapse Interactions. Neuron 2017, 96, 697-708. [CrossRef] [PubMed] · DOI
  33. Baldwin, K.T.; Eroglu, C. Molecular mechanisms of astrocyte-induced synaptogenesis. Curr. Opin. Neurobiol. 2017, 45, 113-120. [CrossRef] [PubMed] · DOI
  34. Lee, J.-H.; Kim, J.-Y.; Noh, S.; Lee, H.; Lee, S.Y.; Mun, J.Y.; Park, H.; Chung, W.-S. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis. Nat. Cell Biol. 2020, 1-6. [CrossRef] · DOI
  35. Jung, Y.-J.; Chung, W.-S. Phagocytic Roles of Glial Cells in Healthy and Diseased Brains. Biomol. Ther. 2018, 26, 350-357. [CrossRef] · DOI · Paper page
  36. Sweeney, M.D.; Zhao, Z.; Montagne, A.; Nelson, A.R.; Zlokovic, B.V. Blood-Brain Barrier: From Physiology to Disease and Back. Physiol. Rev. 2019, 99, 21-78. [CrossRef] · DOI · Paper page
  37. Liebner, S.; Dijkhuizen, R.M.; Reiss, Y.; Plate, K.H.; Agalliu, D.; Constantin, G. Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol. 2018, 135, 311-336. [CrossRef] [PubMed] · DOI · Paper page
  38. Nortley, R.; Attwell, D. Control of brain energy supply by astrocytes. Curr. Opin. Neurobiol. 2017, 47, 80-85. [CrossRef] · DOI
  39. Pellerin, L.; Magistretti, P.J. Sweet Sixteen for ANLS. Br. J. Pharm. 2011, 32, 1152-1166. [CrossRef] [PubMed] · DOI
  40. Iliff, J.J.; Wang, M.; Liao, Y.; Plogg, B.A.; Peng, W.; Gundersen, G.A.; Benveniste, H.; Vates, G.E.; Deane, R.; Goldman, S.A.; et al. A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Inluding Amyloid β. Sci. Transl. Med. 2012, 15, 147ra111. [CrossRef] · DOI · Paper page
  41. Nedergaard, M. Garbage Truck of the Brain. Science 2013, 340, 1529-1530. [CrossRef] [PubMed] · DOI
  42. Oberheim, N.A.; Wang, X.; Goldman, S.; Nedergaard, M. Astrocytic Complexity Distinguishes the Human Brain. Trends Neurosci. 2006, 29, 547-553. [CrossRef] · DOI · Paper page
  43. Bushong, E.A.; Martone, M.E.; Jones, Y.Z.; Ellisman, M.H. Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains. J. Neurosci. 2002, 22, 183-192. [CrossRef] [PubMed] · DOI · Paper page
  44. Oberheim, N.A.; Takano, T.; Han, X.; He, W.; Lin, J.H.C.; Wang, F.; Xu, Q.; Wyatt, J.D.; Pilcher, W.; Ojemann, J.G.; et al. Uniquely Hominid Features of Adult Human Astrocytes. J. Neurosci. 2009, 29, 3276-3287. [CrossRef] · DOI · Paper page
  45. Falcone, C.; Penna, E.; Hong, T.; Tarantal, A.F.; Hof, P.R.; Hopkins, W.D.; Sherwood, C.C.; Noctor, S.C.; Martínez-Cerdeño, V. Cortical Interlaminar Astrocytes Are Generated Prenatally, Mature Postnatally, and Express Unique Markers in Human and Nonhuman Primates. Cereb. Cortex 2021, 31, 379-395. [CrossRef] [PubMed] · DOI · Paper page
  46. Colombo, J.; Quinn, B.; Puissant, V. Disruption of astroglial interlaminar processes in Alzheimer's disease. Brain Res. Bull. 2002, 58, 235-242. [CrossRef] · DOI · Paper page
  47. Sosunov, A.A.; Wu, X.; Tsankova, N.M.; Guilfoyle, E.; McKhann, G.M.; Goldman, J.E. Phenotypic Heterogeneity and Plasticity of Isocortical and Hippocampal Astrocytes in the Human Brain. J. Neurosci. 2014, 34, 2285-2298. [CrossRef] · DOI · Paper page
  48. Kettenmann, H.; Verkhratsky, A. Glial cells. In Neuroscience in the 21st Century: From Basic to Clinical; Springer: New York, NY, USA, 2013; pp. 475-506. [CrossRef] · DOI · Paper page
  49. Escartin, C.; Guillemaud, O.; Sauvage, M.C. Questions and (some) answers on reactive astrocytes. Glia 2019, 67, 2221-2247. [CrossRef] [PubMed] · DOI · Paper page
  50. Jahn, H.M.; Kasakow, C.V.; Helfer, A.; Michely, J.; Verkhratsky, A.; Maurer, H.H.; Scheller, A.; Kirchhoff, F. Refined protocols of tamoxifen injection for inducible DNA recombination in mouse astroglia. Sci. Rep. 2018, 8, 1-11. [CrossRef] · DOI
  51. Yu, X.; Nagai, J.; Khakh, B.S. Improved tools to study astrocytes. Nat. Rev. Neurosci. 2020, 21, 121-138. [CrossRef] · DOI · Paper page
  52. Chai, H.; Diaz-Castro, B.; Shigetomi, E.; Monte, E.; Octeau, J.C.; Yu, X.; Cohn, W.; Rajendran, P.S.; Vondriska, T.M.; Whitelegge, J.P.; et al. Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence. Neuron 2017, 95, 531-549. [CrossRef] [PubMed] · DOI · Paper page
  53. Lin, J.C.C.; Yu, K.; Hatcher, A.; Huang, T.W.; Lee, H.K.; Carlson, J.; Weston, M.C.; Chen, F.; Zhang, Y.; Zhu, W.; et al. Identification of Diverse Astrocyte Populations and Their Malignant Analogs. Nat. Neurosci. 2017, 20, 396-405. [CrossRef] · DOI
  54. Morel, L.; Chiang, M.S.R.; Higashimori, H.; Shoneye, T.; Iyer, L.K.; Yelick, J.; Tai, A.; Yang, Y. Molecular and Functional Properties of Regional Astrocytes in the Adult Brain. J. Neurosci. 2017, 37, 8706-8717. [CrossRef] · DOI · Paper page
  55. Lanjakornsiripan, D.; Pior, B.J.; Kawaguchi, D.; Furutachi, S.; Tahara, T.; Katsuyama, Y.; Suzuki, Y.; Fukazawa, Y.; Gotoh, Y. Layer-Specific Morphological and Molecular Differences in Neo-cortical Astrocytes and Their Dependence on Neuronal Layers. Nat. Commun. 2015, 9, 1623. [CrossRef] · DOI
  56. Morel, L.; Men, Y.; Chiang, M.S.R.; Tian, Y.; Jin, S.; Yelick, J.; Higashimori, H.; Yang, Y. Intracortical astrocyte subpopulations defined by astrocyte reporter Mice in the adult brain. Glia 2019, 67, 171-181. [CrossRef] [PubMed] · DOI · Paper page
  57. Bayraktar, O.A.; Bartels, T.; Holmqvist, S.; Kleshchevnikov, V.; Martirosyan, A.; Polioudakis, D.; Ben Haim, L.; Young, A.M.H.; Batiuk, M.Y.; Prakash, K.; et al. Astrocyte Layers in the Mammalian Cerebral Cortex Revealed by a Single-Cell in Situ Tran- scriptomic Map. Nat. Neurosci. 2020, 23, 500-509. [CrossRef] [PubMed] · DOI · Paper page
  58. Batiuk, M.Y.; Martirosyan, A.; Wahis, J.; de Vin, F.; Marneffe, C.; Kusserow, C.; Koeppen, J.; Viana, J.F.; Oliveira, J.F.; Voet, T.; et al. Identification of Region-Specific Astrocyte Subtypes at Single Cell Resolution. Nat. Commun. 2020, 11, 1-15. [CrossRef] · DOI · Paper page
  59. Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer's disease at 25 years. Embo Mol. Med. 2016, 8, 595-608. [CrossRef] · DOI · Paper page
  60. De Strooper, B.; Karran, E. The Cellular Phase of Alzheimer's Disease. Cell 2016, 164, 603-615. [CrossRef] [PubMed] · DOI · Paper page
  61. Dubois, B.; Hampel, H.; Feldman, H.H.; Scheltens, P.; Aisen, P.; Andrieu, S.; Bakardjian, H.; Benali, H.; Bertram, L.; Blennow, K.; et al. Preclinical Alzheimer's Disease: Definition, Natural History, and Diagnostic Criteria. Alzheimer's Dement. 2016, 12, 292-323. [CrossRef] [PubMed] · DOI · Paper page
  62. Frere, S.; Slutsky, I. Alzheimer's Disease: From Firing Instability to Homeostasis Network Collapse. Neuron 2018, 97, 32-58. [CrossRef] · DOI
  63. Verkhratsky, A.; Zorec, R.; Rodríguez, J.J.; Parpura, V. Astroglia dynamics in ageing and Alzheimer's disease. Curr. Opin. Pharm. 2016, 26, 74-79. [CrossRef] · DOI
  64. Arranz, A.M.; De Strooper, B. The Role of Astroglia in Alzheimer's Disease: Pathophysi-ology and Clinical Implications. Lancet Neurol. 2019, 18, 406-414. [CrossRef] · DOI
  65. Yu, J.-T.; Tan, L.; Hardy, J. Apolipoprotein E in Alzheimer's Disease: An Update. Annu. Rev. Neurosci. 2014, 37, 79-100. [CrossRef] [PubMed] · DOI · Paper page
  66. Holtzman, D.M.; Bales, K.R.; Tenkova, T.; Fagan, A.M.; Parsadanian, M.; Sartorius, L.J.; Mackey, B.; Olney, J.; McKeel, D.; Wozniak, D.; et al. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 2000, 97, 2892-2897. [CrossRef] · DOI · Paper page
  67. Verghese, P.B.; Castellano, J.M.; Garai, K.; Wang, Y.; Jiang, H.; Shah, A.; Bu, G.; Frieden, C.; Holtzman, D.M. ApoE Influences Amyloid-β (Aβ) Clearance despite Minimal ApoE/Aβ As-sociation in Physiological Conditions. Proc. Natl. Acad. Sci. USA 2013, 110, 1807-1816. [CrossRef] · DOI · Paper page
  68. Carter, S.F.; Scholl, M.; Almkvist, O.; Wall, A.; Engler, H.; Langstrom, B.; Nordberg, A. Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Com-bining 11C-Pittsburgh Compound B and 18F-FDG. J. Nucl. Med. 2012, 53, 37-46. [CrossRef] · DOI · Paper page
  69. Rodriguez-Vieitez, E.; Saint-Aubert, L.; Carter, S.F.; Almkvist, O.; Farid, K.; Schöll, M.; Chiotis, K.; Thordardottir, S.; Graff, C.; Wall, A.; et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain 2016, 139, 922-936. [CrossRef] · DOI
  70. Scholl, M.; Carter, S.F.; Westman, E.; Rodriguez-Vieitez, E.; Almkvist, O.; Thordardottir, S.; Wall, A.; Graff, C.; Långstrom, B.; Nordberg, A. Early Astrocytosis in Autosomal Dominant Alzheimer's Disease Measured in Vivo by MultiTracer Positron Emission Tomography. Sci. Rep. 2015, 5, 1-14. [CrossRef] · DOI
  71. Serrano-Pozo, A.; Muzikansky, A.; Gómez-Isla, T.; Growdon, J.H.; Betensky, R.A.; Frosch, M.P.; Hyman, B.T. Differential Relationships of Reactive Astrocytes and Microglia to Fibrillar Amyloid Deposits in Alzheimer Disease. J. Neuropathol. Exp. Neurol. 2013, 72, 462-471. [CrossRef] [PubMed] · DOI · Paper page
  72. Escartin, C.; Galea, E.; Lakatos, A.; O'Callaghan, J.P.; Petzold, G.C.; Serrano-Pozo, A.; Steinhäuser, C.; Volterra, A.; Carmignoto, G.; Agarwal, A.; et al. Reactive astrocyte nomenclature, definitions, and future directions. Nat. Neurosci. 2021, 1-14. [CrossRef] · DOI · Paper page
  73. Beach, T.; McGeer, E. Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex. Brain Res. 1988, 463, 357-361. [CrossRef] · DOI
  74. Rodríguez, J.J.; Olabarria, M.; Chvatal, A.; Verkhratsky, A.; Rodr, J.J. Astroglia in dementia and Alzheimer's disease. Cell Death Differ. 2008, 16, 378-385. [CrossRef] [PubMed] · DOI
  75. Verkhratsky, A.; Zorec, R.; Parpura, V. Stratification of Astrocytes in Healthy and Dis-eased Brain. Brain Pathol. 2017, 27, 629-644. [CrossRef] [PubMed] · DOI · Paper page
  76. Alberdi, E.; Wyssenbach, A.; Alberdi, M.; Sanchez-Gomez, M.V.; Cavaliere, F.; Rodriguez, J.J.; Verkhratsky, A.; Matute, C. Ca(2+)-dependent endoplasmic reticulum stress correlates with astrogliosis in oligomeric amyloid beta-treated astrocytes and in a model of Alzheimer's disease. Aging Cell 2013, 12, 292-302. [CrossRef] · DOI
  77. Kraft, A.W.; Hu, X.; Yoon, H.; Yan, P.; Xiao, O.; Wang, Y.; Gil, S.H.; Brown, J.; Wilhelmsson, U.; Restivo, J.L.; et al. Attenuating Astrocyte Activation Accelerates Plaque Pathogenesis in APP/PS1 Mice. FASEB J. 2013, 27, 187-198. [CrossRef] · DOI · Paper page
  78. Agulhon, C.; Sun, M.-Y.; Murphy, T.; Myers, T.; Lauderdale, K.; Fiacco, T. Calcium Signal-ing and Glio-transmission in Normal vs. Reactive Astrocytes. Front. Pharmacol. 2012, 3, 139. [CrossRef] · DOI · Paper page
  79. Kuchibhotla, K.V.; Lattarulo, C.R.; Hyman, B.T.; Bacskai, B.J. Synchronous hyperactivi-ty and intercellular calcium waves in astrocytes in Alzheimer mice. Science 2009, 323, 1211-1215. [CrossRef] · DOI · Paper page
  80. Frost, G.R.; Li, Y.-M. The Role of Astrocytes in Amyloid Production and Alzheimer's Disease. Open Biol. 2017, 7, 170228. [CrossRef] · DOI
  81. Verkhratsky, A.; Rodríguez-Arellano, J.; Parpura, V.; Zorec, R. Astroglial calcium signalling in Alzheimer's disease. Biochem. Biophys. Res. Commun. 2017, 483, 1005-1012. [CrossRef] · DOI · Paper page
  82. Hsu, E.T.; Gangolli, M.; Su, S.; Holleran, L.; Stein, T.D.; Alvarez, V.E.; McKee, A.C.; Schmidt, R.E.; Brody, D.L. Astrocytic degeneration in chronic traumatic encephalopathy. Acta Neuropathol. 2018, 136, 955-972. [CrossRef] · DOI
  83. Yeh, C.-Y.; Vadhwana, B.; Verkhratsky, A.; Rodriguez, J.J. Early Astrocytic Atrophy in the Entorhinal Cortex of a Triple Transgenic Animal Model of Alzheimer's Disease. ASN Neuro 2011, 3, AN20110025. [CrossRef] [PubMed] · DOI
  84. Olabarria, M.; Noristani, H.N.; Verkhratsky, A.; Rodríguez, J.J. Age-Dependent Decrease in Glutamine Synthetase Expression in the Hippocampal Astroglia of the Triple Transgenic Alzheimer's Disease Mouse Model: Mechanism for Deficient Glutamatergic Transmission? Mol. Neurodegener. 2011, 6, 55. [CrossRef] · DOI
  85. Beauquis, J.; Vinuesa, A.; Pomilio, C.; Pavía, P.; Galván, V.; Saravia, F. Neuronal and Glial Alterations, Increased Anxiety, and Cognitive Impairment before Hippocampal Amyloid Deposition in PDAPP Mice, Model of Alzheimer's Disease. Hippocampus 2014, 24, 257-269. [CrossRef] [PubMed] · DOI
  86. Diniz, L.P.; Tortelli, V.; Matias, I.; Morgado, J.; Araujo, A.P.B.; Melo, H.M.; Da Silva, G.S.S.; Alves-Leon, S.V.; De Souza, J.M.; Ferreira, S.T.; et al. Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model. J. Neurosci. 2017, 37, 6797-6809. [CrossRef] · DOI · Paper page
  87. Iram, T.; Trudler, D.; Kain, D.; Kanner, S.; Galron, R.; Vassar, R.; Barzilai, A.; Blinder, P.; Fishelson, Z.; Frenkel, D. Astrocytes from old Alzheimer's disease mice are impaired in Aβ uptake and in neuroprotection. Neurobiol. Dis. 2016, 96, 84-94. [CrossRef] [PubMed] · DOI
  88. Polis, B.; Srikanth, K.D.; Elliott, E.; Gil-Henn, H.; Samson, A.O. L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of Alzheimer's Disease. Neurotherapeutics 2018, 15, 1036-1054. [CrossRef] · DOI
  89. Jones, V.C.; Atkinson-Dell, R.; Verkhratsky, A.; Mohamet, L. Aberrant iPSC-Derived Human Astrocytes in Alzheimer's Disease. Cell Death Dis. 2017, 8, e2696. [CrossRef] [PubMed] · DOI · Paper page
  90. Chen, A.; Akinyemi, R.O.; Hase, Y.; Firbank, M.J.; Ndung'U, M.N.; Foster, V.; Craggs, L.J.L.; Washida, K.; Okamoto, Y.; Thomas, A.J.; et al. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. Brain 2016, 139, 242-258. [CrossRef] · DOI · Paper page
  91. Ries, M.; Sastre, M. Mechanisms of Aβ Clearance and Degradation by Glial Cells. Front. Aging Neurosci. 2016, 8, 160. [CrossRef] · DOI · Paper page
  92. Lin, Y.-T.; Seo, J.; Gao, F.; Feldman, H.M.; Wen, H.-L.; Penney, J.; Cam, H.P.; Gjoneska, E.; Raja, W.K.; Cheng, J.; et al. APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types. Neuron 2018, 98, 1141-1154. [CrossRef] · DOI · Paper page
  93. Simonovitch, S.; Schmukler, E.; Bespalko, A.; Iram, T.; Frenkel, D.; Holtzman, D.M.; Masliah, E.; Michaelson, D.M.; Pinkas- Kramarski, R. Impaired Autophagy in APOE4 Astrocytes. J. Alzheimer's Dis. 2016, 51, 915-927. [CrossRef] · DOI · Paper page
  94. Huynh, T.-P.V.; Liao, F.; Francis, C.M.; Robinson, G.O.; Serrano, J.R.; Jiang, H.; Roh, J.; Finn, M.B.; Sullivan, P.M.; Esparza, T.J.; et al. Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis. Neuron 2017, 96, 1013-1023.e4. [CrossRef] · DOI · Paper page
  95. Liu, C.-C.; Zhao, N.; Fu, Y.; Wang, N.; Linares, C.; Tsai, C.-W.; Bu, G. ApoE4 Accelerates Early Seeding of Amyloid Pathology. Neuron 2017, 96, 1024-1032.e3. [CrossRef] · DOI · Paper page
  96. Montagne, A.; Nation, D.A.; Sagare, A.P.; Barisano, G.; Sweeney, M.D.; Chakhoyan, A.; Pachicano, M.; Joe, E.; Nelson, A.R.; D'Orazio, L.M.; et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nat. Cell Biol. 2020, 581, 71-76. [CrossRef] [PubMed] · DOI · Paper page
  97. Lian, H.; Zheng, H. Signaling Pathways Regulating Neuron-Glia Interaction and Their Implications in Alzheimer's Disease. J. Neurochem. 2016, 136, 475-491. [CrossRef] [PubMed] 100. · DOI
  98. Lian, H.; Yang, L.; Cole, A.; Sun, L.; Chiang, A.C.A.; Fowler, S.W.; Shim, D.J.; Rodriguez-Rivera, J.; Taglialatela, G.; Jankowsky, J.L.; et al. NFkB-Activated Astroglial Re-lease of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease. Neuron 2015, 85, 101-115. [CrossRef] 101. Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.-S.; Peterson, T.C.; et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017, 541, 481-487. [CrossRef] 102. Jo, S.; Yarishkin, O.; Hwang, Y.J.; Chun, Y.E.; Park, M.; Woo, D.H.; Bae, J.Y.; Kim, T.; Lee, J.; Chun, H.; et al. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease. Nat. Med. 2014, 20, 886-896. [CrossRef] 103. Ghatak, S.; Dolatabadi, N.; Trudler, D.; Zhang, X.; Wu, Y.; Mohata, M.; Ambasudhan, R.; Talantova, M.; Lipton, S.A. Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. Elife 2019, 8, e50333. [CrossRef] [PubMed] 104. Garaschuk, O.; Verkhratsky, A. GABAergic astrocytes in Alzheimer's disease. Aging 2019, 11, 1602-1604. [CrossRef] 105. Chun, H.; Im, H.; Kang, Y.J.; Kim, Y.; Shin, J.H.; Won, W.; Lim, J.; Ju, Y.; Park, Y.M.; Kim, S.; et al. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer's disease via H2O2-production. Nat. Neurosci. 2020, 23, 1555-1566. [CrossRef] [PubMed] 106. Kapogiannis, D.; Mattson, M.P. Disrupted energy metabolism and neuronal circuit dys-function in cognitive impairment and Alzheimer's disease. Lancet Neurol. 2011, 10, 187-198. [CrossRef] 107. Swerdlow, R.H. Mitochondria and Mitochondrial Cascades in Alzheimer's Disease. J. Alzheimer's Dis. 2018, 62, 1403-1416. [CrossRef] 108. Wang, W.; Zhao, F.; Ma, X.; Perry, G.; Zhu, X. Mitochondria dysfunction in the pathogenesis of Alzheimer's disease: Recent advances. Molecular Neurodegeneration 2020, 15, 30. [CrossRef] 109. · DOI · Paper page
  99. Bubber, P.; Haroutunian, V.; Fisch, G.; Blass, J.P.; Gibson, G.E. Mitochondrial abnor-malities in Alzheimer brain: Mechanistic implications. Ann. Neurol. 2005, 57, 695-703. [CrossRef] 110. · DOI · Paper page
  100. Brooks, W.M.; Lynch, P.J.; Ingle, C.C.; Hatton, A.; Emson, P.C.; Faull, R.L.; Starkey, M.P. Gene expression profiles of metabolic enzyme transcripts in Alzheimer's disease. Brain Res. 2007, 1127, 127-135. [CrossRef] 111. · DOI
  101. Adav, S.S.; Park, J.E.; Sze, S.K. Quantitative profiling brain proteomes revealed mito-chondrial dysfunction in Alzheimer's disease. Mol. Brain 2019, 12, 8. [CrossRef] [PubMed] 112. · DOI
  102. Sekar, S.; McDonald, J.; Cuyugan, L.; Aldrich, J.; Kurdoglu, A.; Adkins, J.; Serrano, G.; Beach, T.G.; Craig, D.W.; Valla, J.; et al. Alzheimer's Disease Is Associated with Altered Expression of Genes Involved in Immune Response and Mitochondrial Processes in As-trocytes. Neurobiol. Aging 2015, 36, 583-591. [CrossRef] [PubMed] 113. · DOI · Paper page
  103. Grubman, A.; Chew, G.; Ouyang, J.F.; Sun, G.; Choo, X.Y.; McLean, C.; Simmons, R.K.; Buckberry, S.; Vargas-Landin, D.B.; Poppe, D.; et al. A Single-Cell Atlas of Entorhinal Cortex from Individuals with Alzheimer's Disease Reveals Cell-Type-Specific Gene Expression Regulation. Nat. Neurosci. 2019, 22, 2087-2097. [CrossRef] [PubMed] 114. Sarkar, P.; Zaja, I.; Bienengraeber, M.; Rarick, K.R.; Terashvili, M.; Canfield, S.; Falck, J.R.; Harder, D.R. Epoxyeicosatrienoic acids pretreatment improves amyloid beta-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes. Am. J. Physiol.-Heart Circ. Physiol. 2014, 306, 475-484. [CrossRef] 115. Kaminsky, Y.G.; Kosenko, E.A. Effects of amyloid-beta peptides on hydrogen peroxide-metabolizing enzymes in rat brain in vivo. Free Radic. Res. 2008, 42, 564-573. [CrossRef] 116. Lee, H.P.; Pancholi, N.; Esposito, L.; Previll, L.A.; Wang, X.; Zhu, X.; Smith, M.A.; Lee, H.G. Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mito-chondrial superoxide dismutase activity. PLoS ONE 2012, 7, e28033. [CrossRef] 117. Abramov, A.Y.; Canevari, L.; Duchen, M.R. β-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J. Neurosci. 2004, 24, 565-575. [CrossRef] [PubMed] 118. · DOI · Paper page
  104. Genda, E.N.; Jackson, J.G.; Sheldon, A.L.; Locke, S.F.; Greco, T.M.; O'Donnell, J.C.; Spruce, L.A.; Xiao, R.; Guo, W.; Putt, M.; et al. Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J. Neurosci. 2011, 31, 18275-18288. [CrossRef] 119. Jackson, J.G.; O'Donnell, J.C.; Takano, H.; Coulter, D.A.; Robinson, M.B. Neuronal ac-tivity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. J. Neurosci. 2014, 34, 1613-1624. [CrossRef] [PubMed] 120. Schmukler, E.; Solomon, S.; Simonovitch, S.; Goldshmit, Y.; Wolfson, E.; Michaelson, D.M.; Pinkas-Kramarski, R. Altered mitochondrial dynamics and function in APOE4-expressing astrocytes. Cell Death Dis. 2020, 11, 578. [CrossRef] 121. · DOI · Paper page
  105. Davis, C.-H.O.; Kim, K.-Y.; Bushong, E.A.; Mills, E.A.; Boassa, D.; Shih, T.; Kinebuchi, M.; Phan, S.; Zhou, Y.; Bihlmeyer, N.A.; et al. Transcellular degradation of axonal mitochondria. Proc. Natl. Acad. Sci. USA 2014, 111, 9633-9638. [CrossRef] 122. Hayakawa, K.; Esposito, E.; Wang, X.; Terasaki, Y.; Liu, Y.; Xing, C.; Ji, X.; Lo, E.H. Transfer of mitochondria from astrocytes to neurons after stroke. Nat. Cell Biol. 2016, 535, 551-555. [CrossRef] [PubMed] 123. Morales, I.; Sanchez, A.; Puertas-Avendano, R.; Rodriguez-Sabate, C.; Perez-Barreto, A.; Rodriguez, M. Neuroglial transmitophagy and Parkinson's disease. Glia 2020, 68, 2277-2299. [CrossRef] 124. Gu, X.-L.; Long, C.-X.; Sun, L.; Xie, C.; Lin, X.; Cai, H. Astrocytic expression of Parkinson's disease-related A53T α-synuclein causes neurodegeneration in mice. Mol. Brain 2010, 3, 12. [CrossRef] [PubMed] 125. · DOI
  106. Solano, R.M.; Casarejos, M.J.; Menéndez-Cuervo, J.; Rodriguez-Navarro, J.A.; De Yébenes, J.G.; Mena, M.A. Glial Dysfunction in Parkin Null Mice: Effects of Aging. J. Neurosci. 2008, 28, 598-611. [CrossRef] 126. Yun, S.P.; Kam, T.-I.; Panicker, N.; Kim, S.; Oh, Y.; Park, J.-S.; Kwon, S.-H.; Park, Y.J.; Karuppagounder, S.S.; Park, H.; et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat. Med. 2018, 24, 931-938. [CrossRef] [PubMed] 127. Diaz-Castro, B.; Gangwani, M.R.; Yu, X.; Coppola, G.; Khakh, B.S. Astrocyte molecular signatures in Huntington's disease. Sci. Transl. Med. 2019, 11, eaaw8546. [CrossRef] [PubMed] 128. · DOI · Paper page
  107. Tong, X.; Ao, Y.; Faas, G.C.; Nwaobi, S.E.; Xu, J.; Haustein, M.D.; Anderson, M.A.; Mody, I.; Olsen, M.L.; Sofro-niew, M.V.; et al. Astrocyte Kir4.1 Ion Channel Deficits Con-tribute to Neuronal Dysfunction in Huntington's Disease Model Mice. Nat. Neurosci. 2014, 17, 694-703. [CrossRef] [PubMed] 129. · DOI · Paper page
  108. Alami, N.O.; Schurr, C.; Heuvel, F.O.; Tang, L.; Li, Q.; Tasdogan, A.; Kimbara, A.; Nettekoven, M.; Ottaviani, G.; Raposo, C.; et al. NF-κB Activation in Astrocytes Drives a Stage-specific Beneficial Neuroimmunological Response in ALS. EMBO J. 2018, 37, e98697. [CrossRef] 130. · DOI
  109. Wheeler, M.A.; Quintana, F.J. Regulation of Astrocyte Functions in Multiple Sclerosis. Cold Spring Harbor Perspect. Med. 2019, 9, a029009. [CrossRef] 131. Di Giorgio, F.P.; Carrasco, M.A.; Siao, M.S.; Maniatis, T.; Eggan, K. Non-Cell Autono-mous Effect of Glia on Motor Neurons in an Embryonic Stem Cell-Based ALS Model. Nat. Neurosci. 2007, 10, 608-614. [CrossRef] 132. Gomez-Arboledas, A.; Davila, J.C.; Sanchez-Mejias, E.; Navarro, V.; Nuñez-Diaz, C.; Sanchez-Varo, R.; Sanchez-Mico, M.V.; Trujillo-Estrada, L.; Fernandez-Valenzuela, J.J.; Vizuete, M.; et al. Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease. Glia 2018, 66, 637-653. [CrossRef] 133. Orre, M.; Kamphuis, W.; Osborn, L.M.; Jansen, A.H.; Kooijman, L.; Bossers, K.; Hol, E.M. Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction. Neurobiol. Aging 2014, 35, 2746-2760. [CrossRef] [PubMed] 134. Pan, J.; Ma, N.; Yu, B.; Zhang, W.; Wan, J. Transcriptomic profiling of microglia and astrocytes throughout aging. J. Neuroinflamma- tion 2020, 17, 1-19. [CrossRef] [PubMed] 135. Srinivasan, K.; Friedman, B.A.; Larson, J.L.; Lauffer, B.E.; Goldstein, L.D.; Appling, L.L.; Borneo, J.; Poon, C.; Ho, T.; Cai, F.; et al. Untangling the Brain's Neuroinflammatory and Neurodegenerative Transcrip-tional Responses. Nat. Commun. 2016, 7, 11295. [CrossRef] 136. Simpson, J.E.; Ince, P.G.; Shaw, P.J.; Heath, P.R.; Raman, R.; Garwood, C.J.; Gelsthorpe, C.; Baxter, L.; Forster, G.; Matthews, F.E.; et al. Microarray analysis of the astrocyte transcriptome in the aging brain: Relationship to Alzheimer's pathology and APOE genotype. Neurobiol. Aging 2011, 32, 1795-1807. [CrossRef] [PubMed] 137. · DOI
  110. Mills, J.D.; Nalpathamkalam, T.; Jacobs, H.I.; Janitz, C.; Merico, D.; Hu, P.; Janitz, M. RNA-Seq analysis of the parietal cortex in Alzheimer's disease reveals alternatively spliced isoforms related to lipid metabolism. Neurosci. Lett. 2013, 536, 90-95. [CrossRef] [PubMed] 138. Habib, N.; McCabe, C.; Medina, S.; Varshavsky, M.; Kitsberg, D.; Dvir-Szternfeld, R.; Green, G.; Dionne, D.; Nguyen, L.; Marshall, J.L.; et al. Disease-associated astrocytes in Alzheimer's disease and aging. Nat. Neurosci. 2020, 23, 701-706. [CrossRef] 139. Zhou, Y.; Song, W.M.; Andhey, P.S.; Swain, A.; Levy, T.; Miller, K.R.; Poliani, P.L.; Cominelli, M.; Grover, S.; Gilfillan, S.; et al. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease. Nat. Med. 2020, 26, 131-142. [CrossRef] 140. Mathys, H.; Davila-Velderrain, J.; Peng, Z.; Gao, F.; Mohammadi, S.; Young, J.Z.; Menon, M.; He, L.; Abdurrob, F.; Jiang, X.; et al. Single-cell transcriptomic analysis of Alzheimer's disease. Nature 2019, 570, 332-337. [CrossRef] 141. · DOI · Paper page
  111. Leng, K.; Li, E.; Eser, R.; Piergies, A.; Sit, R.; Tan, M.; Neff, N.; Li, S.H.; Rodriguez, R.D.; Suemoto, C.K.; et al. Molecular characterization of selectively vulnerable neurons in Alzheimer's disease. Nat. Neurosci. 2021, 24, 276-287. [CrossRef] 142. Keren-Shaul, H.; Spinrad, A.; Weiner, A.; Matcovitch-Natan, O.; Dvir-Szternfeld, R.; Ulland, T.K.; David, E.; Baruch, K.; Lara- Astaiso, D.; Toth, B.; et al. A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. Cell 2017, 169, 1276-1290.e17. [CrossRef] 143. Shin, Y.J.; Kang, S.W.; Jeong, S.Y.; Shim, Y.J.; Kim, Y.H.; Kim, B.M.; Kee, S.H.; Park, J.J.; Park, I.S.; Min, B.H. Clusterin Enhances Proliferation of Primary Astrocytes through Extracellular Signal-Regulated Kinase Activation. NeuroReport 2006, 17, 1871-1875. [CrossRef] 144. Kajiwara, Y.; Wang, E.; Wang, M.; Sin, W.C.; Brennand, K.J.; Schadt, E.; Naus, C.C.; Buxbaum, J.; Zhang, B. GJA1 (connexin43) is a key regulator of Alzheimer's disease pathogenesis. Acta Neuropathol. Commun. 2018, 6, 1-20. [CrossRef] 145. Chen, W.-T.; Lu, A.; Craessaerts, K.; Pavie, B.; Frigerio, C.S.; Corthout, N.; Qian, X.; Laláková, J.; Kühnemund, M.; Voytyuk, I.; et al. Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease. Cell 2020, 182, 976-991.e19. [CrossRef] [PubMed] 146. · DOI · Paper page
  112. Prokop, S.; Miller, K.R.; Labra, S.R.; Pitkin, R.M.; Hoxha, K.; Narasimhan, S.; Changolkar, L.; Rosenbloom, A.; Lee, V.M.Y.; Trojanowski, J.Q. Impact of TREM2 Risk Variants on Brain Region-Specific Immune Activation and Plaque Microenvironment in Alzheimer's Disease Pa-tient Brain Samples. Acta Neuropathol. 2019, 138, 613-630. [CrossRef] [PubMed] 147. · DOI · Paper page
  113. Johnson, E.C.B.; Dammer, E.B.; Duong, D.M.; Ping, L.; Zhou, M.; Yin, L.; Higginbotham, L.A.; Guajardo, A.; White, B.; Troncoso, J.C.; et al. Large-scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat. Med. 2020, 26, 769-780. [CrossRef] 148. Klein, H.U.; Schäfer, M.; Bennett, D.A.; Schwender, H.; de Jager, P.L. Bayesian Integra-tive Analysis of Epigenomic and Transcriptomic Data Identifies Alzheimer's Disease Candidate Genes and Networks. PLoS Comput. Biol. 2020, 16, e10007771. [CrossRef] [PubMed] 149. Swarup, V.; Chang, T.S.; Duong, D.M.; Dammer, E.B.; Dai, J.; Lah, J.J.; Johnson, E.C.; Seyfried, N.T.; Levey, A.I.; Geschwind, D.H. Identification of Conserved Proteomic Networks in Neurodegenerative Dementia. Cell Rep. 2020, 31, 107807. [CrossRef] [PubMed] · DOI · Paper page

Cited by

Sorted by citations

Authors
Preman, P., Alfonso-Triguero, M., Alberdi, E., Verkhratsky, A., & Arranz, A. M.
Affiliations
  • VIB-KU Leuven Center for Brain & Disease Research (BE)
  • University of the Basque Country (ES)
  • Ikerbasque (ES)
Corresponding author
Arranz, Amaia M
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-02-09
Volume
10
Issue
3
Pages
540-540
ISSN
2073-4409 (ISSN-L)
DOI
10.20944/preprints202102.0230.v1
PMC
PMC7999452
OpenAlex
W3135516129
Cited by
176
References
0
Citations by year
2026: 31 · 2025: 44 · 2024: 32 · 2023: 32 · 2022: 29 · 2021: 8
FWCI
3.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • Communities in ADDI (Universidad del Pais Vasco) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Hispana (submittedVersion, cc-by)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • Ministerio de Ciencia e Innovación (RTI2018)
  • Agencia Estatal de Investigación
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
astrocytes, Alzheimer's disease, neurodegeneration, molecular pathways, astrocyte morphology, pathogenesis, gene expression changes
MeSH terms
Alzheimer Disease, Astrocytes, Humans, Transcriptome

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