Beta amyloid is neurotoxic in hippocampal slice cultures.
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.
Department of Neurological Surgery, University of Washington, Seattle 98195-6470, USA.
M R
MR
Harrigan
D D
DD
Kunkel
L B
LB
Nguyen
A T
AT
Malouf
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D046508:Culture Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)