Amyloid β protein (Aβ) removal by neuroglial cells in culture

Lillian M. Shaffer, Michael D. Dority, Rekha Gupta-Bansal, Robert C.A. Frederickson, Steven G. Younkin, Kurt R. Brunden

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Because the mechanisms of Aβ degradation in normal and Alzheimer's disease brain are poorly understood, we have examined whether various cortical cells are capable of processing this peptide. Rat microglia and astrocytes, as well as the human THP-1 monocyte cell line, degraded Aβ1-42 added to culture medium. In contrast, neither rat cortical neurons or meningeal fibroblasts effectively catabolized this peptide. When Aβ fibrils were immobilized as plaque-like deposits on culture dishes, both microglia and THP-1 cells removed the peptide. Astrocytes were incapable of processing the Aβ deposits, but these cells released glycosaminoglycase-sensitive molecules that inhibited the subsequent removal of Aβ by microglia. This implied that astrocyte-derived proteoglycans associated with the amyloid peptide and slowed its degradation. The addition of purified proteoglycan to Aβ that was in medium or focally deposited also resulted in significant inhibition of peptide removal by microglia. These data suggest that Aβ can be catabolized by microglia and proteoglycans which co-localize with senile plaques may slow the degradation of Aβ within these pathologic bodies.

Original languageEnglish (US)
Pages (from-to)737-745
Number of pages9
JournalNeurobiology of aging
Volume16
Issue number5
DOIs
StatePublished - Jan 1 1995

Keywords

  • Alzheimer's disease
  • Amyloid β peptide (Aβ)
  • Astrocytes
  • Aβ-binding proteins
  • Microglia
  • Proteoglycans
  • Senile plaques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Shaffer, L. M., Dority, M. D., Gupta-Bansal, R., Frederickson, R. C. A., Younkin, S. G., & Brunden, K. R. (1995). Amyloid β protein (Aβ) removal by neuroglial cells in culture. Neurobiology of aging, 16(5), 737-745. https://doi.org/10.1016/0197-4580(95)00055-J