BETA-AMYLOID IS NEUROTOXIC IN HIPPOCAMPAL SLICE CULTURES

We examined the neurotoxicity of the 40 amino acid fragment of beta am yloid peptide (A beta 1-40) in cultured hippocampal slices. When injec ted into area CA3, A beta 1-40 produced widespread neuronal damage. In jection of the reverse sequence peptide, A beta 40-1, or vehicle alone produced little damage. The distribution A beta 1-40 was highly corre lated with the area of neuronal damage. Thioflavine S and electron mic roscopic analysis confirmed that injected A beta 1-40 formed 7-9 nm AD type amyloid fibrils in the cultures. A beta 1-40 also altered the nu mber of GFAP immunoreactive astrocytes and ED-1 immunoreactive microgl ia/macrophages within and around the A beta 1-40 deposit. The observed neurotoxicity of A beta 1-40 in hippocampal slice cultures provides e vidence that this peptide may be responsible for the neurodegeneration observed in AD.