Harrigan M R, Kunkel D D, Nguyen L B, Malouf A T
Department of Neurological Surgery, University of Washington, Seattle 98195-6470, USA.
Neurobiol Aging. 1995 Sep-Oct;16(5):779-89. doi: 10.1016/0197-4580(95)00095-v.
We examined the neurotoxicity of the 40 amino acid fragment of beta amyloid peptide (A beta 1-40) in cultured hippocampal slices. When injected into area CA3, A beta 1-40 produced widespread neuronal damage. Injection of the reverse sequence peptide, A beta 40-1, or vehicle alone produced little damage. The distribution A beta 1-40 was highly correlated with the area of neuronal damage. Thioflavine S and electron microscopic 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 number of GFAP immunoreactive astrocytes and ED-1 immunoreactive microglia/macrophages within and around the A beta 1-40 deposit. The observed neurotoxicity of A beta 1-40 in hippocampal slice cultures provides evidence that this peptide may be responsible for the neurodegeneration observed in AD.
