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Astroglial atrophy in Alzheimer’s disease

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Abstract

Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration and death of neurones. In Alzheimer’s disease (AD), astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; downregulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cell-specific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting, or even curing AD-linked neurodegeneration.

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Funding

AV and AS were supported by Volkswagen Stiftung research grant A115105; RZ by Slovenian Research Agency Research core funding no. P3 310 and projects no. J3 6790, no. J3 9266 and no. J3 7605. AS was supported by COMFI grant 17-00-00412 (K)/17-00-00409 from RFBR and ; AV and AP were supported by the Global Grant measure (No. 09.3.3-LMT-K-712-01-0082).

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Authors and Affiliations

  1. Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    Alexei Verkhratsky

  2. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky

  3. BioCruces Health Research Institute, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Jose Julio Rodrigues

  4. Department of Neuroscience, The University of the Basque Country UPV/EHU, Plaza de Cruces 12, 48903, Barakaldo, Bizkaia, Spain

    Jose Julio Rodrigues

  5. Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Santariškių street 5, LT-08406, Vilnius, Lithuania

    Augustas Pivoriunas

  6. Medical Faculty, Institute of Pathophysiology, Laboratory of Neuroendocrinology and Molecular Cell Physiology, University of Ljubljana, Zaloska cesta 4, SI-1000, Ljubljana, Slovenia

    Robert Zorec

  7. Celica, BIOMEDICAL, Technology Park 24, 1000, Ljubljana, Slovenia

    Robert Zorec

  8. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya street 16/10, Moscow, 117997, Russia

    Alexey Semyanov

  9. Sechenov First Moscow State Medical University, Bolshaya Pirogovskaya street 19с1, Moscow, 119146, Russia

    Alexey Semyanov

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  1. Alexei Verkhratsky
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Verkhratsky, A., Rodrigues, J.J., Pivoriunas, A. et al. Astroglial atrophy in Alzheimer’s disease. Pflugers Arch - Eur J Physiol 471, 1247–1261 (2019). https://doi.org/10.1007/s00424-019-02310-2

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