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Cited by 71Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Reactive astrocytes as treatment targets in Alzheimer's disease—Systematic review of studies using the APPswePS1dE9 mouse model

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Smit, Tamar, Deshayes, Natasja A. C., Borchelt, David R., Kamphuis, Willem, Middeldorp, Jinte, Hol, Elly M.·2021·Glia
DOI 10.1002/glia.23981PMC PMC8247905
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Abstract

Astrocytes regulate synaptic communication and are essential for proper brain functioning. In Alzheimer's disease (AD) astrocytes become reactive, which is characterized by an increased expression of intermediate filament proteins and cellular hypertrophy. Reactive astrocytes are found in close association with amyloid‐beta (Aβ) deposits. Synaptic communication and neuronal network function could be directly modulated by reactive astrocytes, potentially contributing to cognitive decline in AD. In this review, we focus on reactive astrocytes as treatment targets in AD in the APPswePS1dE9 AD mouse model, a widely used model to study amyloidosis and gliosis. We first give an overview of the model; that is, how it was generated, which cells express the transgenes, and the effect of its genetic background on Aβ pathology. Subsequently, to determine whether modifying reactive astrocytes in AD could influence pathogenesis and cognition, we review studies using this mouse model in which interventions were directly targeted at reactive astrocytes or had an indirect effect on reactive astrocytes. Overall, studies specifically targeting astrocytes to reduce astrogliosis showed beneficial effects on cognition, which indicates that targeting astrocytes should be included in developing novel therapies for AD.

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Authors
Smit, T., Deshayes, N. A. C., Borchelt, D. R., Kamphuis, W., Middeldorp, J., & Hol, E. M.
Affiliations
  • Utrecht University (NL)
  • University of Florida Health (US)
  • Netherlands Institute for Neuroscience (NL)
Corresponding author
Hol, Elly M.
ORCID
Venue
Glia
Publisher
Wiley
Published
2021-02-25
Volume
69
Issue
8
Pages
1852-1881
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
DOI
10.1002/glia.23981
PMC
PMC8247905
OpenAlex
W3129946102
Cited by
71
References
237
Citations by year
2026: 9 · 2025: 12 · 2024: 17 · 2023: 9 · 2022: 16 · 2021: 8
FWCI
1.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Glia (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, other-oa)
Funders
  • Alzheimer Nederland (WE.03‐2017‐04)
  • National Institute on Aging (P50AG047266)
  • ZonMw (733050504, 733050505, 733050816)
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
reactive astrocytes, Alzheimer's disease, astrocyte activation, amyloid-beta, amyloidosis, cognitive decline, astrocyte-targeted therapy, intermediate filament proteins, astrocyte hypertrophy, genetic background effects
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Disease Models, Animal, Gliosis, Mice, Transgenic, Amyloid beta-Peptides, Mice

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