{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:27:15Z","timestamp":1791023235024,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,12,9]],"date-time":"2004-12-09T00:00:00Z","timestamp":1102550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The formation of neurotoxic beta\u2010amyloid fibrils in Alzheimer's disease (AD) is suggested to involve membrane rafts and to be promoted, <jats:italic>in\u2003vitro<\/jats:italic>, by enriched concentrations of gangliosides, particularly GM1, and the cholesterol therein. In our study, the presence of rafts and their content of the major membrane lipids and gangliosides in the temporal cortex, reflecting late stages of AD pathology, and the frontal cortex, presenting earlier stages, has been investigated. Whole tissue and isolated detergent\u2010resistant membrane fractions (DRMs) were analysed from 10 AD and 10 age\u2010matched control autopsy brains. DRMs from the frontal cortex of AD brains contained a significantly higher concentration (\u00b5mol\/\u00b5mol glycerophospholipids), of ganglioside GM1 (22.3\u2003\u00b1\u20034.6 compared to 10.3\u2003\u00b1\u20036.4, <jats:italic>p<\/jats:italic>\u2003&lt;\u20030.001) and GM2 (2.5\u2003\u00b1\u20031.0 compared to 0.55\u2003\u00b1\u20030.3, <jats:italic>p<\/jats:italic>\u2003&lt;\u20030.001). Similar increases of these gangliosides were also seen in DRMs from the temporal cortex of AD brains, which, in addition, comprised significantly lower proportions of DRMs. Moreover, these remaining rafts were depleted in cholesterol (from 1.5\u2003\u00b1\u20030.2 to 0.6\u2003\u00b1\u20030.3\u2003\u00b5mol\/\u00b5mol glycerophospholipids, <jats:italic>p<\/jats:italic>\u2003&lt;\u20030.001). In summary, we found an increased proportion of GM1 and GM2 in DRMs, and accelerating plaque formation at an early stage, which may gradually lead to membrane raft disruptions and thereby affect cellular functions associated with the presence of such membrane domains.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02849.x","type":"journal-article","created":{"date-parts":[[2006,3,3]],"date-time":"2006-03-03T12:19:40Z","timestamp":1141388380000},"page":"171-182","source":"Crossref","is-referenced-by-count":189,"title":["Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent\u2010resistant membrane domains"],"prefix":"10.1111","volume":"92","author":[{"given":"Marie","family":"Molander\u2010Melin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"Bogdanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Dellheden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Eric","family":"M\u00e5nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam","family":"Fredman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,9]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688184"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068886"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(83)90043-8"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1991.00530220048018"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.930060306"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90189-J"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04839.x"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.37.22987"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(94)90110-4"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(58)90025-1"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610298005110"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(91)90272-E"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207113"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(03)00025-7"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610296002736"},{"key":"e_1_2_18_17_1","first-page":"461","article-title":"New directions in cancer therapy based on aberrant expression of glycosphingolipids: anti\u2010adhesion and ortho\u2010signaling therapy","volume":"3","author":"Hakomori S.","year":"1991","journal-title":"Cancer Cells"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026524820177"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91592-5"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100252200"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0255874"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00386-3"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(90)90026-T"},{"key":"e_1_2_18_24_1","first-page":"37","article-title":"The role of 24 hydroxycholesterol in Alzheimer's disease","volume":"7","author":"Kolsch H.","year":"2003","journal-title":"J. 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