title: Deposits of A beta fibrils are not toxic to cortical and hippocampal neurons in vitro.
abstract: Amyloid beta peptide (A beta), which is deposited as insoluble fibrils in senile plaques, is thought to play a role in the neuropathology of Alzheimer's disease. We have developed a model in which rat embryonic cerebral cortical or hippocampal neurons are seeded onto culture dishes containing deposits of substrate-bound, fibrillar A beta. The neurons attached rapidly to A beta 1-40 and A beta 1-42 substrates and extended long, branching neurites. Quantitative assessment demonstrated that survival of neurons on the A beta matrices was equivalent to or better than on control substrates of poly L-lysine or poly L-ornithine. In contrast, preparations of A beta fibrils added directly to the culture medium caused neuronal death as previously reported in the literature. These results reveal that the response of neurons to deposited A beta 1-40 and A beta 1-42 is substantially different from that observed with suspensions of the amyloid peptides, with the former serving as growth-promoting substrates for cortical and hippocampal neurons. This may thus imply that fibrillar A beta of senile plaques is not sufficient by itself to cause the plaque-associated neuronal degeneration characteristic of AD.
authors.affiliation: Gliatech Incorporated, Cleveland, OH 44122, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Wujek
authors.forename: M D
authors.initials: MD
authors.lastname: Dority
authors.forename: R C
authors.initials: RC
authors.lastname: Frederickson
authors.forename: K R
authors.initials: KR
authors.lastname: Brunden
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009410:Nerve Degeneration; D051381:Rats; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor