Transforming growth factor-β protects human neurons against β-amyloid-induced injury

Chun C. Chao, Shuxian Hu, Frederic H. Kravitz, Monica Tsang, W. Robert Anderson, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Deposition of amyloid fibrils in the brain is a histopathologic hallmark of Alzheimer disease (AD) and β-amyloid protein (Aβ), the principal component of amyloid fibrils, has been implicated in the neuropathogenesis of AD. In the present study, we first developed an in vitro model of Aβ-induced neurodegeneration using human fetal brain-cell cultures and then tested the hypothesis that cytokines modulate Aβ-induced neurodegeneration. When brain-cell cultures were exposed to Aβ, marked neuronal loss (60% of neurons by microscopic assessment) and functional impairment (i.e., reduction in uptake of [3H]γ-aminobutryric acid) were observed after 6 d of incubation. Aβ-induced neurodegeneration was dose-dependent with maximal effect at 100 μM. Although interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α had a nominal effect, both the β1 and β2 isoforms of transforming growth factor-β dose-dependently protected >50% of neurons against Aβ-induced injury. IL-4 also proved to be neuroprotective. Aβ-induced neurodegeneration was accompanied by microglial cell proliferation and enhanced release of IL-1, IL-6, and TNF-α. These findings are consistent with the emerging concept that AD is an inflammatory disease and may lead to new therapeutic strategies aimed at reducing Aβ-induced neurotoxicity.

Original languageEnglish (US)
Pages (from-to)159-178
Number of pages20
JournalMolecular and Chemical Neuropathology
Issue number2-3
StatePublished - Oct 1994


  • Neurodegeneration
  • interleukin-4
  • microglia
  • transforming growth factor-β
  • β-amyloid


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