{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:21:31Z","timestamp":1791271291743,"version":"4.1.0"},"reference-count":75,"publisher":"Society for Neuroscience","issue":"22","license":[{"start":{"date-parts":[[2006,11,30]],"date-time":"2006-11-30T00:00:00Z","timestamp":1164844800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2006,5,31]]},"abstract":"<jats:p>\n                    Characterization of soluble oligomeric amyloid \u03b2 (A\u03b2) species in the brains of Alzheimer's disease (AD) patients and transgenic models has raised the possibility that different conformations of A\u03b2 may contribute to AD pathology via different mechanisms. To characterize the toxic effect of different A\u03b2 conformations, we tested side by side the effect of well characterized A\u03b2 oligomers (A\u03b2Os), A\u03b2-derived diffusible ligands (ADDLs), and fibrillar A\u03b2 (A\u03b2f) preparations in human cortical neurons (HCNs). Both A\u03b2Os and ADDLs bind rapidly and with high affinity to synaptic contacts and cellular membranes. A\u03b2Os (5 \u03bc\n                    <jats:sc>m<\/jats:sc>\n                    ) induced rapid and massive neuronal death. Calcium influx accelerated, but was not required for, A\u03b2O toxicity. A\u03b2Os elicited a stereotyped succession of cellular changes consistent with the activation of a mitochondrial death apoptotic pathway. At low concentrations A\u03b2Os caused chronic and subtler mitochondrial alterations but minimal cell death. ADDLs induced similar toxic changes as A\u03b2Os but on a fivefold longer time scale. Higher concentrations of A\u03b2f and longer incubation times were required to produce widespread neuritic dystrophy but modest HCN cell death. Thus various A\u03b2 species may play relevant roles in AD, causing neurotoxicity by distinct non-overlapping mechanisms affecting neuronal function and viability over multiple time courses.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1189-06.2006","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T19:15:20Z","timestamp":1149102920000},"page":"6011-6018","source":"Crossref","is-referenced-by-count":429,"title":["Different Conformations of Amyloid \u03b2 Induce Neurotoxicity by Distinct Mechanisms in Human Cortical 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