Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.

The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (A beta P) contributes to this degeneration. We now report that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with A beta Ps exhibit morphological and biochemical characteristics of apoptosis, including membrane blebbing, compaction of nuclear chromatin, and internucleosomal DNA fragmentation.

Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state.

The progressive neurodegeneration of Alzheimer's disease has been hypothesized to be mediated, at least in part, by beta-amyloid protein. A relationship between the aggregation state of beta-amyloid protein and its ability to promote degeneration in vitro has been previously suggested. To evaluate this hypothesis and to define a structure-activity relationship for beta-amyloid, aggregation properties of an overlapping series of synthetic beta-amyloid peptides (beta APs) were investigated and compared with beta AP neurotoxic properties in vitro.

In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity.

beta-Amyloid peptide forms the senile plaques of Alzheimer's disease and has been previously demonstrated to have both trophic and toxic effects on neurons in vitro. We report here that synthetic beta-amyloid peptide shows both aggregation and neurotoxicity after a 2-4 day incubation period, but is neurite-promoting and not toxic in its initially solubilized state. SDS-PAGE characterization shows that newly solubilized beta-amyloid is predominantly monomeric whereas incubated peptide has several high molecular weight species.

Type II glucocorticoid receptors are expressed in oligodendrocytes and astrocytes.

Glucocorticoid hormones affect gene expression directly at the level of transcription via intracellular receptors that translocate to the nucleus in the presence of steroid. In the brain, two types of high-affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II, glucocorticoid receptor (GR). Both receptor types are expressed by many types of neurons.