Astrocytes from old Alzheimer's disease mice are impaired in Aβ uptake and in neuroprotection

Tal Iram, Dorit Trudler, David Kain, Sivan Kanner, Ronit Galron, Robert Vassar, Ari Barzilai, Pablo Blinder, Zvi Fishelson, Dan Frenkel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

In Alzheimer's disease (AD), astrocytes undergo morphological changes ranging from atrophy to hypertrophy, but the effect of such changes at the functional level is still largely unknown. Here, we aimed to investigate whether alterations in astrocyte activity in AD are transient and depend on their microenvironment, or whether they are irreversible. We established and characterized a new protocol for the isolation of adult astrocytes and discovered that astrocytes isolated from old 5xFAD mice have higher GFAP expression than astrocytes derived from WT mice, as observed in vivo. We found high C1q levels in brain sections from old 5xFAD mice in close vicinity to amyloid plaques and astrocyte processes. Interestingly, while old 5xFAD astrocytes are impaired in uptake of soluble Aβ42, this effect was reversed upon an addition of exogenous C1q, suggesting a potential role for C1q in astrocyte-mediated Aβ clearance. Our results suggest that scavenger receptor B1 plays a role in C1q-facilitated Aβ uptake by astrocytes and that expression of scavenger receptor B1 is reduced in adult old 5xFAD astrocytes. Furthermore, old 5xFAD astrocytes show impairment in support of neuronal growth in co-culture and neurotoxicity concomitant with an elevation in IL-6 expression. Further understanding of the impact of astrocyte impairment on AD pathology may provide insights into the etiology of AD.

Original languageEnglish (US)
Pages (from-to)84-94
Number of pages11
JournalNeurobiology of Disease
Volume96
DOIs
StatePublished - Dec 1 2016

Keywords

  • Adult astrocyte culture
  • Alzheimer's disease
  • Aβ uptake
  • C1q
  • Neurotoxicity
  • SR-B1
  • VEGF

ASJC Scopus subject areas

  • Neurology

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