Astrocyte modulation of in vitro beta-amyloid neurotoxicity.

In Alzheimer's disease brain, beta-amyloid (Abeta) deposition is accompanied by astrocyte activation, whose role in the pathogenesis of the disease is still unclear. To explore the subject, we compared Abeta neurotoxicity in pure hippocampal cultures and neuronal-astrocytic cocultures, where astrocytes conditioned neurons but were not in contact with them or Abeta. In the presence of astrocytes, neurons were protected from Abeta neurotoxicity. Neuritic dystrophy was reduced, synapses were partially preserved, and apoptosis was contrasted. The protection disappeared when astrocytes were also treated with Abeta, suggesting that Abeta-astrocyte interaction is deleterious for neurons. This was supported by comparing Abeta neurotoxicity in pure neurons and neurons grown on astrocytes. In this case, where astrocytes were also in contact with Abeta, neuritic damage was enhanced and expression of synaptic vesicle proteins decreased. Our results suggest that astrocytes can protect neurons from Abeta neurotoxicity, but when they interact with Abeta, the protection is undermined and neurotoxicity enhanced. Copyright 2004 Wiley-Liss, Inc.