Beta amyloid is neurotoxic in hippocampal slice cultures

We examined the neurotoxicity of the 40 amino acid fragment of beta amyloid peptide (Aβ1–40) in cultured hippocampal slices. When injected into area CA3, Aβ1–40 produced widespread neuronal damage. Injection of the reverse sequence peptide, Aβ40-1, or vehicle alone produced little damage. The distribution Aβ1–40 was highly correlated with the area of neuronal damage. Thioflavine S and electron microscopic analysis confirmed that injected Aβ1–40 formed 7–9 nm AD type amyloid fibrils in the cultures. Aβ1–40 also altered the number of GFAP immunoreactive astrocytes and ED-1 immunoreactive microglia/macrophages within and around the Aβ1–40 deposit. The observed neurotoxicity of Aβ1–40 in hippocampal slice cultures provides evidence that this peptide may be responsible for the neurodegeneration observed in AD.