{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:48:43Z","timestamp":1773020923944,"version":"3.50.1"},"reference-count":20,"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>The prevalence of known mutations in presenilin genes (PS1 and PS2) causing early\u2010onset familial Alzheimer's disease (FAD) was assessed in a population of 98 singleton early\u2010onset AD cases, 29 early\u2010onset FAD cases, and 15 late\u2010onset FAD cases. None of the cases tested positive for the eight mutations initially reported, and none of these mutations were observed in 60 age\u2010matched controls. A novel mutation (R269H) in PS1 was found in a single case of early\u2010onset AD but not in any other AD or control case. Thus, the PS mutations tested are quite rare in early\u2010onset AD. Amyloid \u03b2 protein (A\u03b2) deposition was investigated in the temporal cortex of the R269H mutation case using end\u2010specific monoclonal antibodies to detect the presence of A\u03b2<jats:sub>x\u221240<\/jats:sub> and A\u03b2<jats:sub>x\u221242<\/jats:sub> subspecies. Stereologically unbiased tangle and neuropil thread counts were obtained from the same region. R269H PS1 mutation was associated with early age of dementia onset, higher amounts of total A\u03b2 and A\u03b2<jats:sub>x\u221242<\/jats:sub>, and increased neuronal cytoskeletal changes. Thus, if the changes observed on this case prove to be typical of PS1 mutations, PS1 mutations may impact both amyloid deposition and neurofibrillary pathology.<\/jats:p>","DOI":"10.1002\/ana.410410618","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:01:22Z","timestamp":1104591682000},"page":"809-813","source":"Crossref","is-referenced-by-count":60,"title":["A novel presenilin\u20101 mutation: Increased \u03b2\u2010amyloid and neurofibrillary changes"],"prefix":"10.1002","volume":"41","author":[{"given":"T.","family":"G\u00f3mez\u2010Isla","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Wasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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