{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:18:13Z","timestamp":1762100293671},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2686,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1997,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations of the presenilin <jats:italic>PS1<\/jats:italic> and <jats:italic>PS2<\/jats:italic> genes are closely linked to aggressive forms of early\u2010onset (&lt;60 years) familial Alzheimer's disease. A highly specific monoclonal antibody was developed to identify and characterize the native PS1 protein. Western blot analyses revealed a predominant 32\u2010kd immunoreactive polypeptide in a variety of samples, including PC12 cells transfected with human <jats:italic>PS1<\/jats:italic> complementary DNA, brain biopsy specimens from demented patients, and postmortem samples of frontal neocortex from early\u2010onset familial Alzheimer's disease cases (<jats:italic>PS1<\/jats:italic> and <jats:italic>PS2<\/jats:italic>), lateonset sporadic Alzheimer's disease cases, and cases of other degenerative disorders. This truncated polypeptide contains the N\u2010terminus of PS1 and appeared unchaged across cases. In 2 early\u2010onset cases linked to missense mutations in the <jats:italic>PS1<\/jats:italic> gene, a PS1 immunoreactive protein (\u223c49 kd) accumulated in the frontal cortex. This protein was similar in size to full\u2010length PS1 protein present in transfected cells overexpressing <jats:italic>PS1<\/jats:italic> complementary DNA, and in lymphocytes from an affected individual with a deletion of exon 9 of the <jats:italic>PS1<\/jats:italic> gene, suggesting that mutations of the <jats:italic>PS1<\/jats:italic> gene perturb the endoproteolytic processing of the protein. Immunohistochemical studies of control brains revealed that PS1 is expressed primarily in neurons, with the protein localized in the soma and dendritic processes. In contrast, PS1 showed striking localization to the neuropathology in early\u2010onset familial Alzheimer's disease and sporadic Alzheimer's disease cases. PS1 immunoreactivity was present in the neuritic component of senile plaques as well as in neurofibrillary tangles. Localization of PS1 immunoreactivity in familial and sporadic Alzheimer's disease suggests that genetically heterogeneous forms of the disease share a common pathophysiology involving PS1 protein.<\/jats:p>","DOI":"10.1002\/ana.410410610","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:01:22Z","timestamp":1104591682000},"page":"742-753","source":"Crossref","is-referenced-by-count":34,"title":["Presenilin\u20101 protein expression in familial and sporadic Alzheimer's disease"],"prefix":"10.1002","volume":"41","author":[{"given":"Allan I.","family":"Levey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig J.","family":"Heilman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James J.","family":"Lah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman R.","family":"Nash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard D.","family":"Rees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Wakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne S.","family":"Mirra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Rye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Nochlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Bird","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(85)90139-8"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.6.980"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.7.1215"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.1.136"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360307"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360308"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925564"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/353844a0"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92809-X"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0995-848a"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-219"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-230"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/376775a0"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92810-3"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199512000-00071"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638621"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.1.55"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/377351a0"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0296-224"},{"key":"e_1_2_1_25_2","unstructured":"LahJ HeilmanC NashN et al. 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