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

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

Research output: Contribution to journalArticlepeer-review

284 Scopus citations

Abstract

β-Amyloid(1-42) (Aβ42), 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, Aβ42-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 Aβ42-positive material and that the amount of this material correlates positively with the extent of local AD pathology. Aβ42-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, alpha7 nicotinic acetylcholine receptor and choline acetyltransferase, in Aβ42-burdened, activated astrocytes supports this possibility. Our results also suggest that some astrocytes containing Aβ42-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, Aβ42 accumulation and the selective lysis of Aβ42-burdened neurons and astrocytes appear to make a major contribution to the observed amyloid plaques in AD brains.

Original languageEnglish (US)
Pages (from-to)197-209
Number of pages13
JournalBrain Research
Volume971
Issue number2
DOIs
StatePublished - May 9 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Molecular Biology
  • Neuroscience(all)
  • Developmental Biology

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