{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:05:07Z","timestamp":1791230707196,"version":"4.1.0"},"reference-count":51,"publisher":"Society for Neuroscience","issue":"20","license":[{"start":{"date-parts":[[2004,11,19]],"date-time":"2004-11-19T00:00:00Z","timestamp":1100822400000},"content-version":"vor","delay-in-days":184,"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":[[2004,5,19]]},"abstract":"<jats:p>A fundamental question about the early pathogenesis of Alzheimer's disease (AD) concerns how toxic aggregates of amyloid \u03b2 protein (A\u03b2) are formed from its nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound A\u03b2 (GA\u03b2) is involved in the process. We now examined this possibility using a novel monoclonal antibody raised against GA\u03b2 purified from an AD brain. Here, we report that GA\u03b2 has a conformation distinct from that of soluble A\u03b2 and initiates A\u03b2 aggregation by acting as a seed. Furthermore, GA\u03b2 generation in the brain was validated by both immunohistochemical and immunoprecipitation studies. These results imply a mechanism underlying the onset of AD and suggest that an endogenous seed can be a target of therapeutic strategy.<\/jats:p>","DOI":"10.1523\/jneurosci.0861-04.2004","type":"journal-article","created":{"date-parts":[[2004,5,19]],"date-time":"2004-05-19T19:48:24Z","timestamp":1084996104000},"page":"4894-4902","source":"Crossref","is-referenced-by-count":225,"title":["A Seed for Alzheimer Amyloid in the Brain"],"prefix":"10.1523","volume":"24","author":[{"given":"Hideki","family":"Hayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyasu","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Yokoseki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Michikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Lemere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Selkoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Naiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Yanagisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2004,5,19]]},"reference":[{"key":"2023041303064706000_24.20.4894.1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2304"},{"key":"2023041303064706000_24.20.4894.2","doi-asserted-by":"publisher","DOI":"10.1038\/78682"},{"key":"2023041303064706000_24.20.4894.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(99)00109-0"},{"key":"2023041303064706000_24.20.4894.4","unstructured":"Binding MM, Jones ST (1996) Rodent to human antibodies by CDR grafting. In: Antibody engineering (Mcmafferty J, Hoogenboon HR, Chiswell DJ, eds), pp 147\u2013168. Oxford: Oxford UP."},{"key":"2023041303064706000_24.20.4894.5","first-page":"173","volume":"29","year":"1991","journal-title":"Eur J Morphol"},{"key":"2023041303064706000_24.20.4894.6","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"2023041303064706000_24.20.4894.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01504-9"},{"key":"2023041303064706000_24.20.4894.8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.37.22987"},{"key":"2023041303064706000_24.20.4894.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature01979"},{"key":"2023041303064706000_24.20.4894.10","doi-asserted-by":"crossref","unstructured":"Ding TT, Harper JD (1999) Analysis of amyloid-\u03b2 assemblies using tapping mode atomic force microscopy under ambient conditions. In: Amyloid, prions, and other proteinaggregates (Wetzel R, ed), pp 510\u2013525. New York: Academic.","DOI":"10.1016\/S0076-6879(99)09035-7"},{"key":"2023041303064706000_24.20.4894.11","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207113"},{"key":"2023041303064706000_24.20.4894.12","doi-asserted-by":"publisher","DOI":"10.1021\/bi992933h"},{"key":"2023041303064706000_24.20.4894.13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.66.1.385"},{"key":"2023041303064706000_24.20.4894.14","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(97)90255-6"},{"key":"2023041303064706000_24.20.4894.15","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(97)90303-3"},{"key":"2023041303064706000_24.20.4894.16","doi-asserted-by":"publisher","DOI":"10.1021\/bi9904149"},{"key":"2023041303064706000_24.20.4894.17","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200203250-00004"},{"key":"2023041303064706000_24.20.4894.18","doi-asserted-by":"publisher","DOI":"10.1038\/nm783"},{"key":"2023041303064706000_24.20.4894.19","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1046\/j.1471-4159.1996.66041717.x","volume":"66","year":"1996","journal-title":"J Neurochem"},{"key":"2023041303064706000_24.20.4894.20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100252200"},{"key":"2023041303064706000_24.20.4894.21","doi-asserted-by":"publisher","DOI":"10.1021\/bi0255874"},{"key":"2023041303064706000_24.20.4894.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00386-3"},{"key":"2023041303064706000_24.20.4894.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079469"},{"key":"2023041303064706000_24.20.4894.24","first-page":"121","volume":"2","year":"1988","journal-title":"Neurosci Res Commun"},{"key":"2023041303064706000_24.20.4894.25","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-730"},{"key":"2023041303064706000_24.20.4894.26","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00052-G"},{"key":"2023041303064706000_24.20.4894.27","doi-asserted-by":"crossref","first-page":"10879","DOI":"10.1523\/JNEUROSCI.23-34-10879.2003","volume":"23","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303064706000_24.20.4894.28","doi-asserted-by":"publisher","DOI":"10.1021\/bi982345o"},{"key":"2023041303064706000_24.20.4894.29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.43.26482"},{"key":"2023041303064706000_24.20.4894.30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.8.4506"},{"key":"2023041303064706000_24.20.4894.31","doi-asserted-by":"publisher","DOI":"10.1038\/nm790"},{"key":"2023041303064706000_24.20.4894.32","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981001)54:1<58::AID-JNR7>3.0.CO;2-G"},{"key":"2023041303064706000_24.20.4894.33","doi-asserted-by":"publisher","DOI":"10.1021\/bi981843u"},{"key":"2023041303064706000_24.20.4894.34","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1999.0744"},{"key":"2023041303064706000_24.20.4894.35","first-page":"374","volume":"74","year":"1996","journal-title":"Lab Invest"},{"key":"2023041303064706000_24.20.4894.36","doi-asserted-by":"publisher","DOI":"10.1021\/bi980550y"},{"key":"2023041303064706000_24.20.4894.37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1600-0684.1998.tb00244.x","volume":"27","year":"1998","journal-title":"J Med Primatol"},{"key":"2023041303064706000_24.20.4894.38","doi-asserted-by":"publisher","DOI":"10.1021\/bi015985r"},{"key":"2023041303064706000_24.20.4894.39","doi-asserted-by":"publisher","DOI":"10.1177\/42.2.8288861"},{"key":"2023041303064706000_24.20.4894.40","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1016\/S0021-9258(18)53661-9","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"2023041303064706000_24.20.4894.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004308200"},{"key":"2023041303064706000_24.20.4894.42","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5300.630"},{"key":"2023041303064706000_24.20.4894.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb13231.x"},{"key":"2023041303064706000_24.20.4894.44","doi-asserted-by":"publisher","DOI":"10.1038\/42408"},{"key":"2023041303064706000_24.20.4894.45","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(74)90093-3"},{"key":"2023041303064706000_24.20.4894.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.4109"},{"key":"2023041303064706000_24.20.4894.47","first-page":"452","volume":"145","year":"1994","journal-title":"Am J Pathol"},{"key":"2023041303064706000_24.20.4894.48","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90236-8"},{"key":"2023041303064706000_24.20.4894.49","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(98)00032-3"},{"key":"2023041303064706000_24.20.4894.50","doi-asserted-by":"publisher","DOI":"10.1038\/nm1095-1062"},{"key":"2023041303064706000_24.20.4894.51","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01484-1"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0861-04.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T13:02:13Z","timestamp":1705150933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0861-04.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,19]]},"references-count":51,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2004,5,19]]},"published-print":{"date-parts":[[2004,5,19]]}},"alternative-id":["10.1523\/JNEUROSCI.0861-04.2004"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0861-04.2004","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,19]]}}}