{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:32:27Z","timestamp":1791952347863,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T00:00:00Z","timestamp":1373846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Early\u2010onset familial Alzheimer disease (AD) is an autosomal dominant disorder caused by mutations in the amyloid precursor protein, presenilin 1 (<jats:italic>PSEN1<\/jats:italic>), or presenilin 2 gene. The objective of this study was to characterize the phenotype in a large family with a <jats:italic>PSEN1<\/jats:italic> F177S mutation by performing detailed clinical assessments, neuroimaging, and neuropathological analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In two subjects, clinical and neuropsychological assessments, structural magnetic resonance imaging, F\u201018\u20102\u2010fluoro\u20102\u2010deoxy\u2010D\u2010glucose positron emission tomographic imaging, AD biomarkers in cerebrospinal fluid and genetic analysis were available. In three deceased affected subjects, medical records were reviewed. In one subject, a complete neuropathological examination was available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cognitive impairment and neurological symptoms developed homogeneously around 30 years of age and worsened rapidly. All subjects died about 7 years (range, 6\u20138 years) after disease onset before 40 years of age. All technical diagnostic information (neuroimaging, cerebrospinal fluid) were typically for AD. Neuropathology showed abundant neuritic plaques and neurofibrillary tangles, typical of severe AD. Antidementia treatment in one subject did not alter the length of survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:italic>PSEN1<\/jats:italic> F177S mutation leads to typical AD starting at age 30 and a homogeneous phenotype with rapid cognitive decline and prominent neurological symptoms. Excessive amyloid beta 42 production in the brain cortex corresponds well with other <jats:italic>PSEN1<\/jats:italic> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2013.02.006","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T19:45:21Z","timestamp":1373571921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical characterization of a presenilin 1 mutation (F177S) in a family with very early\u2010onset Alzheimer's disease in the third decade of life"],"prefix":"10.1002","volume":"10","author":[{"given":"Lucrezia","family":"Hausner","sequence":"first","affiliation":[{"name":"Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim University of Heidelberg Heidelberg Germany"},{"name":"Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob A.","family":"Tsch\u00e4pe","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration and Neurobiology Saarland University Saarbrueckken Germany"},{"name":"Department of Neurology Saarland University Saarbrueckken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Peter","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Central Institute of Mental Health, Medical Faculty Mannheim University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration and Neurobiology Saarland University Saarbrueckken Germany"},{"name":"Department of Neurology Saarland University Saarbrueckken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Fr\u00f6lich","sequence":"additional","affiliation":[{"name":"Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2005.12.001"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/376775a0"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/302553"},{"key":"e_1_2_5_9_2","unstructured":"Alzheimer Disease & Frontotemporal Dementia Mutation Database.Available at:http:\/\/www.molgen.ua.ac.be\/ADMutations\/. 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