Cited by 123Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

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The Many Faces of Astrocytes in Alzheimer's Disease

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Monterey, Michael D., Wei, Haichao, Wu, Xizi, Wu, Jia Qian·2021·Frontiers in Neurology

DOI 10.3389/fneur.2021.619626PMC PMC8438135

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common cause of dementia in an aging population. The majority of research effort has focused on the role of neurons in neurodegeneration and current therapies have limited ability to slow disease progression. Recently more attention has been given to the role of astrocytes in the process of neurodegeneration. Specifically, reactive astrocytes have both advantageous and adverse effects during neurodegeneration. The ability to isolate and depict astrocyte phenotype has been challenging. However, with the recent development of single-cell sequencing technologies researchers are provided with the resource to delineate specific biomarkers associated with reactive astrocytes in AD. In this review, we will focus on the role of astrocytes in normal conditions and the pathological development of AD. We will further review recent developments in the understanding of astrocyte heterogeneity and associated biomarkers. A better understanding of astrocyte contributions and phenotypic changes in AD can ultimately lead to more effective therapeutic targets.

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Figure 1 Examples of roles of astrocytes in normal condition and in AD. The left half of astrocyte (yellow) depicts normal astrocyte functions, including neurotransmitter recycling (U-turn arrow and brown-outlined circles), synaptogenesis, central nerve system (CNS) homeostasis, and interaction with vasculature. The right half of astrocyte (Pink) depicts a reactive astrocyte in Alzheimer's Disease (AD). The black box contains some examples of the astrocytic signaling pathways related to AD. Green box indicates examples of inducing factors of reactive astrocytes from microglia. Red boxes are the representative intracellular and secretory molecules (red-outlined circles) and astrocytic makers expressed by reactive astrocytes in AD. Blue circles with icons are synapses. K+, potassium; AQP4, aquaporin-4; Kir4.1, inwardly rectifying K+ channel subunit 4.1; APP, amyloid-beta precursor protein; BACE1, β-site APP-cleaving enzyme 1; FFA, free fatty acid; GFAP, glial fibrillary acidic protein; YKL-40, chitinase-3 protein like-1; S100B, S100 calcium-binding protein B; MAOB, monoamine-oxidase-b; GLAST, glutamate aspartate transporter; GLT-1, glutamate transporter 1; Ca2+, calcium; NF-κB, nuclear factor- kappa B; Stat3, signal transducer and activator of transcription 3; AGEs, advance glycation end-products; RAGE, Receptor for advanced glycation end products; TGF-β, transforming growth factor beta; GABA, gamma-aminobutyric acid; IL, interleukin; TNF-α, tumor necrosis factor alpha; C1q, complement component 1q.CC BY · PubMed Central

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Additional file 24 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700907
Additional file 16 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700883
Additional file 23 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700904
Additional file 13 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700874
Additional file 4 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700847
Additional file 11 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700868
Additional file 10 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700865
Additional file 18 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700889
Additional file 1 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.25530184
Additional file 15 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700880
Additional file 1 of Amyloid-β specific regulatory T cells attenuate Alzheimer’s disease pathobiology in APP/PS1 mice
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Additional file 22 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700901
Additional file 14 of Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture
Das, D., Sonthalia, S., Stein-O.’Brien, G., Wahbeh, M., Feuer, K., Goff, L. A., Colantuoni, C., Mahairaki, V., & Avramopoulos, D. (2024) · Figshare · doi:10.6084/m9.figshare.26700877
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Authors: Monterey, M. D., Wei, H., Wu, X., & Wu, J. Q.
Affiliations: The University of Texas Health Science Center at Houston (US)
Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Wu, Jia Qian
ORCID: Wei, Haichao
Wu, Jia Qian
Venue: Frontiers in Neurology
Publisher: Frontiers Media SA
Published: 2021-08-31
Volume: 12
Pages: 619626-619626
ISSN: 1664-2295 (ISSN-L)
DOI: 10.3389/fneur.2021.619626
PMC: PMC8438135
OpenAlex: W3197066362
Cited by: 117
References: 127
Citations by year: 2026: 12 · 2025: 27 · 2024: 34 · 2023: 29 · 2022: 15
FWCI: 2.80
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Neurology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
National Eye Institute (R21EY028647)
National Institute of Neurological Disorders and Stroke (R21NS113068, R01NS088353)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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: Alzheimer's disease, astrocytes, reactive astrocytes, astrocyte heterogeneity, neurodegeneration, single-cell sequencing, therapeutic target

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The Many Faces of Astrocytes in Alzheimer's Disease

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