{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:30:41Z","timestamp":1781109041685,"version":"3.54.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,11]]},"abstract":"<jats:p>\n                    Alzheimer's disease (AD) is a neurodegenerative disease with an insidious onset and progressive course that inevitably leads to death. The current diagnostic tools do not allow for diagnosis until the disease has lead to irreversible brain damage. Genetic studies of autosomal dominant early onset familial AD has identified three causative genes: amyloid precursor protein (\n                    <jats:italic>APP<\/jats:italic>\n                    ), presenilin 1 and 2 (\n                    <jats:italic>PSEN1<\/jats:italic>\n                    and\n                    <jats:italic>PSEN2<\/jats:italic>\n                    ). We performed a global gene expression analysis on fibroblasts from 33 individuals (both healthy and demented mutation carriers as well as wild-type siblings) from three families segregating the\n                    <jats:italic>APP<\/jats:italic>\n                    <jats:sub>SWE<\/jats:sub>\n                    ,\n                    <jats:italic>APP<\/jats:italic>\n                    <jats:sub>ARC<\/jats:sub>\n                    and\n                    <jats:italic>PSEN1<\/jats:italic>\n                    H163Y mutations, respectively. The mutations cause hereditary progressive cognitive disorder, including typical autosomal dominant AD. Our data show that the mutation carriers share a common gene expression profile significantly different from that of their wild-type siblings. The results indicate that the disease process starts several decades before the onset of cognitive decline, suggesting that presymptomatic diagnosis of AD and other progressive cognitive disorders may be feasible in the near future.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0504178102","type":"journal-article","created":{"date-parts":[[2005,9,30]],"date-time":"2005-09-30T20:33:39Z","timestamp":1128112419000},"page":"14854-14859","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings"],"prefix":"10.1073","volume":"102","author":[{"given":"Yosuke","family":"Nagasaka","sequence":"first","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Dillner","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayao","family":"Ebise","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiji","family":"Teramoto","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Lilius","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Axelman","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Forsell","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ito","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Winblad","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kimura","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[{"name":"Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan; Department Neurotec, Karolinska Institutet, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Novum Fifth Floor, SE-141 57 Huddinge, Sweden; andDepartment Neurotec, Karolinska Institutet and Karolinska University Hospital, Huddinge Geriatric Medicine, M51, SE-141 86, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,9,30]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_3_2_2_2","unstructured":"World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (WHO Geneva)."},{"key":"e_1_3_2_3_2","unstructured":"American Psychological Association (1994) Diagnostic and Statistical Manual of Mental Disorders (Am. Psychol. Assoc. Washington DC)."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.3.022502.103022"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-345"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-219"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-887"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10351"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200007)48:1<77::AID-ANA12>3.0.CO;2-A"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020952704398"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4968"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/10445490152717541"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1176"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00306-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2004.01.008"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/15216540412331286002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.3.469"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.Supplement_1.1449"},{"key":"e_1_3_2_19_2","first-page":"42","volume":"7","year":"1971","unstructured":"Steinberg, D. (1971) Birth Defects Orig. Artic Ser. 7, 42-52.","journal-title":"Birth Defects Orig. Artic Ser."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1159\/000153018"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600766"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020115"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35021093"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.531"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08270-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1994.00540240037013"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.5.698"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(96)13218-3"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","unstructured":"Jolliffe I. T. (1986) Principal Component Analysis (Springer New York).","DOI":"10.1007\/978-1-4757-1904-8"},{"key":"e_1_3_2_31_2","unstructured":"Vapnik V. N. (1998) Statistical Learning Theory (Wiley New York)."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1936.tb02137.x"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.9.809"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.3.728"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/415530a"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1060"},{"key":"e_1_3_2_39_2","first-page":"3005","volume":"62","year":"2002","unstructured":"Wigle, D. A., Jurisica, I., Radulovich, N., Pintilie, M., Rossant, J., Liu, N., Lu, C., Woodgett, J., Seiden, I., Johnston, M., et al. (2002) Cancer Res. 62, 3005-3008.12036904","journal-title":"Cancer Res."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm843"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0504178102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T13:01:35Z","timestamp":1649768495000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0504178102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9,30]]},"references-count":40,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2005,10,11]]}},"alternative-id":["10.1073\/pnas.0504178102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0504178102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,9,30]]},"assertion":[{"value":"2005-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}