{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T23:07:57Z","timestamp":1776899277516,"version":"3.51.2"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[1996,8,1]],"date-time":"1996-08-01T00:00:00Z","timestamp":838857600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[1996,8]]},"DOI":"10.1038\/nm0896-864","type":"journal-article","created":{"date-parts":[[2004,8,19]],"date-time":"2004-08-19T01:39:14Z","timestamp":1092879554000},"page":"864-870","source":"Crossref","is-referenced-by-count":2064,"title":["Secreted amyloid \u03b2\u2013protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease"],"prefix":"10.1038","volume":"2","author":[{"given":"D.","family":"Scheuner","sequence":"first","affiliation":[]},{"given":"C.","family":"Eckman","sequence":"additional","affiliation":[]},{"given":"M.","family":"Jensen","sequence":"additional","affiliation":[]},{"given":"X.","family":"Song","sequence":"additional","affiliation":[]},{"given":"M.","family":"Citron","sequence":"additional","affiliation":[]},{"given":"N.","family":"Suzuki","sequence":"additional","affiliation":[]},{"given":"T.D.","family":"Bird","sequence":"additional","affiliation":[]},{"given":"J.","family":"Hardy","sequence":"additional","affiliation":[]},{"given":"M.","family":"Hutton","sequence":"additional","affiliation":[]},{"given":"W.","family":"Kukull","sequence":"additional","affiliation":[]},{"given":"E.","family":"Larson","sequence":"additional","affiliation":[]},{"given":"L.","family":"Levy-Lahad","sequence":"additional","affiliation":[]},{"given":"M.","family":"Viitanen","sequence":"additional","affiliation":[]},{"given":"E.","family":"Peskind","sequence":"additional","affiliation":[]},{"given":"P.","family":"Poorkaj","sequence":"additional","affiliation":[]},{"given":"G.","family":"Schellenberg","sequence":"additional","affiliation":[]},{"given":"R.","family":"Tanzi","sequence":"additional","affiliation":[]},{"given":"W.","family":"Wasco","sequence":"additional","affiliation":[]},{"given":"L.","family":"Lannfelt","sequence":"additional","affiliation":[]},{"given":"D.","family":"Selkoe","sequence":"additional","affiliation":[]},{"given":"S.","family":"Younkin","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFnm0896864_CR1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/ana.410370305","volume":"37","author":"T Iwatsubo","year":"1995","unstructured":"Iwatsubo, T., Mann, D.M., Odaka, A., Suzuki, N. & Ihara, Y. Amyloid \u03b2 protein (A\u03b2) deposition: A\u03b2p42(43) precedes A\u03b240 in Down syndrome. Ann. Neurol. 37, 294\u2013299 (1995).","journal-title":"Ann. Neurol."},{"key":"BFnm0896864_CR2","doi-asserted-by":"publisher","first-page":"7013","DOI":"10.1074\/jbc.270.13.7013","volume":"270","author":"SA Gravina","year":"1995","unstructured":"Gravina, S.A. et al. Amyloid beta protein (A\u03b2) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A\u03b240 or A\u03b242(43). J. Biol. Chem. 270, 7013\u20137016 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896864_CR3","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1016\/S0021-9258(18)53661-9","volume":"268","author":"A Roher","year":"1993","unstructured":"Roher, A. et al. Structural alterations in the peptide backbone of \u03b2-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J. Biol. Chem. 268, 3072\u20133083 (1993).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896864_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1006\/abbi.1993.1112","volume":"301","author":"DL Miller","year":"1993","unstructured":"Miller, D.L. et al. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch. Biochem. 301, 41\u201352 (1993).","journal-title":"Arch. Biochem."},{"issue":"6393","key":"BFnm0896864_CR5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/359325a0","volume":"359","author":"Peter Seubert","year":"1992","unstructured":"Seubert, P. et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 359, 325\u2013327 (1992).","journal-title":"Nature"},{"key":"BFnm0896864_CR6","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1126\/science.1439760","volume":"258","author":"M Shoji","year":"1992","unstructured":"Shoji, M. et al. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 258, 126\u2013129 (1992).","journal-title":"Science"},{"key":"BFnm0896864_CR7","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/359322a0","volume":"359","author":"C Haass","year":"1992","unstructured":"Haass, C. et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359, 322\u2013325 (1992).","journal-title":"Nature"},{"key":"BFnm0896864_CR8","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1073\/pnas.90.5.2092","volume":"90","author":"J Busciglio","year":"1993","unstructured":"Busciglio, J., Gabuzda, D.H., Matsudaira, P. & Yankner, B.A. Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc. Natl. Acad. Sci. USA 90, 2092\u20132096 (1993).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0896864_CR9","first-page":"1039","volume":"4","author":"HF Dovey","year":"1993","unstructured":"Dovey, H.F., Suomesaari-Chrysler, S., Lieberburg, I., Sinha, S. & Kiem, P.S. Cells with a familial Alzheimer's disease mutation produce authentic \u03b2-peptide. Neuro Report 4, 1039\u20131042(1993).","journal-title":"Neuro Report"},{"key":"BFnm0896864_CR10","doi-asserted-by":"crossref","unstructured":"Vigo-Pelfrey, C., Lee, D., Keim, P., Lieberburg, I. & Schenk, D.B. Characterization of p amyloid peptide from human cerebrospinal fluid. J. Neurochem. 61, 19965\u201319968 (1993).","DOI":"10.1111\/j.1471-4159.1993.tb09841.x"},{"key":"BFnm0896864_CR11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0022-2836(91)90881-6","volume":"218","author":"C Hilbich","year":"1991","unstructured":"Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C.L. & Beyreuther, K. Aggregation and secondary structure of synthetic amyloid \u03b2A4 peptides of Alzheimer's disease. J. Mol. Biol. 218, 149\u2013163 (1991).","journal-title":"J. Mol. Biol."},{"key":"BFnm0896864_CR12","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S0021-9258(18)48529-8","volume":"267","author":"D Burdick","year":"1992","unstructured":"Burdick, D. et al. Assembly and aggregation properties of synthetic Alzheimer's A4\/\u03b2 amyloid peptide analogs. J. Biol. Chem. 267, 546\u2013554 (1992).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896864_CR13","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","volume":"73","author":"JT Jarrett","year":"1993","unstructured":"Jarrett, J.T. & Lansbury, P.T., Seeding \u201cone-dimensional crystallization\u201d of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73, 1055\u20131058 (1993).","journal-title":"Cell"},{"key":"BFnm0896864_CR14","doi-asserted-by":"publisher","first-page":"4693","DOI":"10.1021\/bi00069a001","volume":"32","author":"JT Jarrett","year":"1993","unstructured":"Jarrett, J.T., Berger, E.P. & Lansbury, P.T., The carboxy terminus of p amyloid protein is critical for the seeding of amyloid formation: Implications for patho-genesis of Alzheimer's disease. Biochemistry 32, 4693\u20134697 (1993).","journal-title":"Biochemistry"},{"key":"BFnm0896864_CR15","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/375754a0","volume":"375","author":"R Sherrington","year":"1995","unstructured":"Sherrington, R. et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754\u2013760 (1995).","journal-title":"Nature"},{"key":"BFnm0896864_CR16","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1126\/science.7638622","volume":"269","author":"E Levy-Lahad","year":"1995","unstructured":"Levy-Lahad, E. et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269, 973\u2013977 (1995).","journal-title":"Science"},{"key":"BFnm0896864_CR17","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1126\/science.7638621","volume":"269","author":"E Levy-Lahad","year":"1995","unstructured":"Levy-Lahad, E. et al. A familial Alzheimer's disease locus on chromosome 1. Science 269, 970\u2013973 (1995).","journal-title":"Science"},{"key":"BFnm0896864_CR18","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/376775a0","volume":"376","author":"E Rogaev","year":"1995","unstructured":"Rogaev, E. et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775\u2013778 (1995).","journal-title":"Nature"},{"key":"BFnm0896864_CR19","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/349704a0","volume":"349","author":"A Goate","year":"1991","unstructured":"Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704\u2013706 (1991).","journal-title":"Nature"},{"key":"BFnm0896864_CR20","doi-asserted-by":"crossref","unstructured":"Naruse, S. et al. Missense mutation Val-Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 337, 978 (1991).","DOI":"10.1016\/0140-6736(91)91612-X"},{"issue":"3","key":"BFnm0896864_CR21","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/0006-291X(91)91011-Z","volume":"178","author":"Katsuji Yoshioka","year":"1991","unstructured":"Yoshioka, K., Miki, T., Katsuya, T., Ogihara, T. & Sakaki, Y. The 717Val-Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem. Biophys. Res. Commun. 178, 1141 (1991).","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"BFnm0896864_CR22","doi-asserted-by":"crossref","unstructured":"Hardy, J. et al. Molecular classification of Alzheimer's disease. Lancet 337, 1342 (1991).","DOI":"10.1016\/0140-6736(91)93011-W"},{"key":"BFnm0896864_CR23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1126\/science.1925564","volume":"254","author":"J Murrell","year":"1991","unstructured":"Murrell, J., Farlow, M., Ghetti, B. & Benson, M.D. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254, 97\u201399 (1991).","journal-title":"Science"},{"key":"BFnm0896864_CR24","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/353844a0","volume":"353","author":"M-C Chartier-Harlin","year":"1991","unstructured":"Chartier-Harlin, M.-C. et al. Early-onset Alzheimer's disease caused by mutations at codon 717 of the \u03b2-amyloid precursor protein gene. Nature 353, 844\u2013846 (1991).","journal-title":"Nature"},{"key":"BFnm0896864_CR25","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng0892-345","volume":"1","author":"M Mullan","year":"1992","unstructured":"Mullan, M. et al. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of \u03b2-amyloid. Nature Genet. 1, 345\u2013347 (1992).","journal-title":"Nature Genet."},{"key":"BFnm0896864_CR26","doi-asserted-by":"publisher","first-page":"11993","DOI":"10.1073\/pnas.91.25.11993","volume":"91","author":"M Citron","year":"1994","unstructured":"Citron, M. et al. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Natl. Acad. Sci. USA 91, 11993\u201311997 (1994).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0896864_CR27","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1126\/science.8424174","volume":"259","author":"XD Cai","year":"1993","unstructured":"Cai, X.D., Golde, T.E. & Younkin, S.G. Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259, 514\u2013516 (1993).","journal-title":"Science"},{"key":"BFnm0896864_CR28","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/360672a0","volume":"360","author":"M Citron","year":"1992","unstructured":"Citron, M. et al. Mutation of the \u03b2-amyloid precursor protein in familial Alzheimer's disease increases p-protein production. Nature 360, 672\u2013674 (1992).","journal-title":"Nature"},{"key":"BFnm0896864_CR29","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1126\/science.8191290","volume":"264","author":"N Suzuki","year":"1994","unstructured":"Suzuki, N. et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (P APP717) mutants. Science 264, 1336\u20131340 (1994).","journal-title":"Science"},{"key":"BFnm0896864_CR30","doi-asserted-by":"crossref","first-page":"32721","DOI":"10.1016\/S0021-9258(20)30050-8","volume":"269","author":"A Tamaoka","year":"1994","unstructured":"Tamaoka, A. et al. APP717 missense mutation affects the ratio of amyloid beta protein species (A\u03b2l-42\/43 and A\u03b21-40) in familial Alzheimer's disease brain. J. Biol. Chem. 269, 32721\u201332724 (1994).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896864_CR31","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/ana.410380413","volume":"38","author":"R Motter","year":"1995","unstructured":"Motter, R. et al. Reduction of beta-amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann. Neurol. 38, 643\u2013648 (1995).","journal-title":"Ann. Neurol."},{"key":"BFnm0896864_CR32","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1056\/NEJM198412133112406","volume":"311","author":"A Grubb","year":"1984","unstructured":"Grubb, A. et al. Abnormal metabolism of gamma-trace alkaline microprotein. The basic defect in hereditary cerebral hemorrhage with amyloidosis. N. Engl. J. Med. 311, 1547\u20131549 (1984).","journal-title":"N. Engl. J. Med."},{"key":"BFnm0896864_CR33","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/372092a0","volume":"372","author":"J Ma","year":"1994","unstructured":"Ma, J., Yee, A., Brewer, H.B., Jr., Das, S. & Potter, H. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372, 92\u201394 (1994).","journal-title":"Nature"},{"key":"BFnm0896864_CR34","first-page":"1030","volume":"145","author":"T Wisniewski","year":"1994","unstructured":"Wisniewski, T., Castano, E.M., Golabek, A., Vogel, T. & Frangione, B. Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. Am. J. Pathol. 145, 1030\u20131035 (1994).","journal-title":"Am. J. Pathol."},{"key":"BFnm0896864_CR35","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1042\/bj3060599","volume":"306","author":"E Casta\u00f1o","year":"1995","unstructured":"Casta\u00f1o, E. et al. Fibrillogenesis in Alzheimer's disease of the amyloid beta peptides and apolipoprotein E. Biochem. J. 306, 599\u2013604 (1995).","journal-title":"Biochem. J."},{"key":"BFnm0896864_CR36","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1073\/pnas.92.3.763","volume":"92","author":"KC Evans","year":"1995","unstructured":"Evans, K.C., Berger, E.P., Cho, C.G., Weisgraber, K.H. & Lansbury, P.T., Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: Implications for the pathogenesis and treatment of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 92, 763\u2013767 (1995).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0896864_CR37","first-page":"404","volume":"2","author":"EB Larson","year":"1990","unstructured":"Larson, E.B. et al. University of Washington Alzheimer's Disease Patient Registry (ADPR): 1987\u20131988. Aging 2, 404\u2013408 (1990).","journal-title":"Aging"},{"key":"BFnm0896864_CR38","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/oxfordjournals.aje.a117370","volume":"141","author":"WA Kukull","year":"1995","unstructured":"Kukull, W.A. et al. Solvent exposure as a risk factor for Alzheimer's disease: A case-control study. Am. J. Epidemiol. 141, 1059\u20131071 (1995); (erratum) Am. J. Epidemiol. 142, 450 (1996).","journal-title":"Am. J. Epidemiol."},{"key":"BFnm0896864_CR39","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1212\/WNL.34.7.939","volume":"34","author":"G McKhann","year":"1984","unstructured":"McKhann, G. et al. Clinical diagnosis of Alzheimer's disease: Report of the NINCSDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 34, 939\u2013944 (1984).","journal-title":"Neurology"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0896-864","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0896-864.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0896-864.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:30:45Z","timestamp":1684452645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm0896-864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1996,8]]}},"alternative-id":["BFnm0896864"],"URL":"https:\/\/doi.org\/10.1038\/nm0896-864","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,8]]}}}