NEURITE GROWTH-INHIBITORY PROPERTIES OF AMYLOID BETA-PEPTIDES IN-VITRO - A-BETA-25-35, BUT NOT A-BETA-1-40, IS INHIBITORY

The effects of freshly-solubilized synthetic amyloid beta-peptides on the growth of neurites from high density cultures of embryonic chick d orsal root ganglia and retinal pieces over periods of 24 to 48 hours w ere examined. The undecapeptide beta 25-35, the presumed neurotoxic mo iety of beta 1-40, was found to inhibit neurite outgrowth, whereas bet a 1-40 and beta 1-28 were without effect. The growth-inhibitory effect of beta 25-35 was apparent at a concentration of 10 ng/ml and showed concentration dependence. The inhibitory effect was reversible, since dorsal root ganglia grown initially in beta 25-35-supplemented medium showed more extensive neurite outgrowth when transferred to normal gro wth medium after 24 hours than dorsal root ganglia maintained in fresh ly-made beta 25-35-supplemented medium throughout. It is concluded tha t beta 25-35 has neurite growth-inhibitory properties in vitro not sha red by beta 1-40 or beta 1-28. The differences in peptide behaviour ma y be related to aggregation state. These findings may have implication s for understanding plaque morphology in normal ageing and Alzheimer's disease, since N-terminally truncated amyloid beta-peptides are prefe rentially localized in the diffuse plaques which lack a surrounding ne uritic reaction; this may also indicate a physiological neurite growth -inhibitory activity for N-terminally truncated amyloid beta-peptides.