Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains

Nagele, Robert G.; D’Andrea, Michael R.; Lee, H.; Venkataraman, Venkateswar; Wang, Hoau-Yan

doi:10.1016/s0006-8993(03)02361-8

Cited by 416Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains

Nagele, Robert G., D’Andrea, Michael R., Lee, H., Venkataraman, Venkateswar, Wang, Hoau-Yan·2003·Brain Research

DOI 10.1016/s0006-8993(03)02361-8

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Abstract

beta-Amyloid(1-42) (A beta 42), a major component of amyloid plaques, accumulates within pyramidal neurons in the brains of individuals with Alzheimer's disease (AD) and Down syndrome. In brain areas exhibiting AD pathology, A beta 42-immunopositive material is observed in astrocytes. In the present study, single- and double-label immunohistochemistry were used to reveal the origin and fate of this material in astrocytes. Our findings suggest that astrocytes throughout the entorhinal cortex of AD patients gradually accumulate A beta 42-positive material and that the amount of this material correlates positively with the extent of local AD pathology. A beta 42-positive material within astrocytes appears to be of neuronal origin, most likely accumulated via phagocytosis of local degenerated dendrites and synapses, especially in the cortical molecular layer. The co-localization of neuron-specific proteins, alpha 7 nicotinic acetylcholine receptor and choline acetyltransferase, in A beta 42-burdened, activated astrocytes supports this possibility. Our results also suggest that some astrocytes containing A beta 42-positive deposits undergo lysis, resulting in the formation of astrocyte-derived amyloid plaques in the cortical molecular layer in brain regions showing moderate to advanced AD pathology. These astrocytic plaques can be distinguished from those arising from neuronal lysis by virtue of their smaller size, their nearly exclusive localization in the subpial portion of the molecular layer of the cerebrocortex, and by their intense glial fibrillary acidic protein immunoreactivity. Overall, A beta 42 accumulation and the selective lysis of A beta 42-burdened neurons and astrocytes appear to make a major contribution to the observed amyloid plaques in AD brains.

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Astrocytes are involved in the clearance of Aβ through the BBB via the AQP4 channels expressed in their end feet and are also able to phagocytose amyloid.
“astrocytes are involved in the clearance of Aβ through the BBB via the AQP4 channels expressed in their end feet and are also able to phagocytose amyloid [6, 34, 35].”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [34]
In AD patients, astrocytes in the entorhinal cortex accumulate Aβ, this accumulation being positively correlated with the extent of AD.
“In AD patients, astrocytes in the entorhinal cortex accumulate Aβ, this accumulation being positively correlated with the extent of AD (Nagele et al., 2003).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Nagele et al., 2003

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Authors: Nagele, R. G., D’Andrea, M. R., Lee, H., Venkataraman, V., & Wang, H.-Y.
Affiliations: University of Medicine and Dentistry of New Jersey (US)
Rutgers, The State University of New Jersey (US)
City University of New York (US)
Corresponding author: Nagele, Robert G.
ORCID: Nagele, Robert G.
Wang, Hoau-Yan
Venue: Brain Research
Publisher: Elsevier BV
Published: 2003-05
Volume: 971
Issue: 2
Pages: 197-209
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/s0006-8993(03)02361-8
OpenAlex: W2022127378
Cited by: 416
References: 63
Citations by year: 2026: 8 · 2025: 21 · 2024: 19 · 2023: 32 · 2022: 21 · 2021: 41 · 2020: 26 · 2019: 17 · 2018: 21 · 2017: 24 · 2016: 23 · 2015: 26 · 2014: 17 · 2013: 13 · 2012: 17
FWCI: 5.74
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG00925)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, amyloid-beta 42, astrocytes, entorhinal cortex, phagocytosis, alpha7 nicotinic acetylcholine receptor, choline acetyltransferase, glial fibrillary acidic protein, Down syndrome
MeSH terms: Aged, Alzheimer Disease, Astrocytes, Choline O-Acetyltransferase, Female, Glial Fibrillary Acidic Protein, Humans, Male, Neurons, Peptide Fragments, Receptors, Nicotinic, Case-Control Studies, Amyloid beta-Peptides, Entorhinal Cortex, Plaque, Amyloid, alpha7 Nicotinic Acetylcholine Receptor

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Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains

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