{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:57:40Z","timestamp":1790621860330,"version":"4.1.0"},"reference-count":18,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dement Geriatr Cogn Disord"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>&lt;i&gt;Background\/Aims:&lt;\/i&gt; Oligomeric amyloid \u03b2 (A\u03b2) is currently considered to induce Alzheimer\u2019s disease (AD). We examined 2 patients with familial AD who possessed the Osaka (E693\u0394) mutation in amyloid precursor protein. To the best of our knowledge, these patients are the first AD cases presumably affected with A\u03b2 oligomers in the absence of senile plaques, and they support the A\u03b2 oligomer hypothesis. &lt;i&gt;Methods:&lt;\/i&gt; We evaluated the clinical course, neuropsychological data, cerebrospinal fluid biomarker levels, magnetic resonance imaging (MRI) scans, fluorodeoxyglucose-positron emission tomography (PET) scans, and Pittsburgh compound B (PiB)-PET images of these patients. &lt;i&gt;Results:&lt;\/i&gt; In the early stages, these patients developed memory disturbances in a similar rate to patients with sporadic AD. Despite their memory disturbances, both patients showed only limited brain atrophy on MRI and little amyloid accumulation on PiB-PET. Subsequent to the development of memory disturbances, both patients suffered from motor dysfunction, probably due to cerebellar ataxia, and, within a few years, the patients fell into an apallic state. &lt;i&gt;Conclusions:&lt;\/i&gt; Familial AD patients with Osaka (E693\u0394) mutation show severe dementia, cerebellar ataxia, and gait disturbances.<\/jats:p>","DOI":"10.1159\/000330017","type":"journal-article","created":{"date-parts":[[2011,8,15]],"date-time":"2011-08-15T06:41:23Z","timestamp":1313390483000},"page":"45-54","source":"Crossref","is-referenced-by-count":45,"title":["Clinical Course of Patients with Familial Early-Onset Alzheimer\u2019s Disease Potentially Lacking Senile Plaques Bearing the E693\u0394 Mutation in Amyloid Precursor Protein"],"prefix":"10.1159","volume":"32","author":[{"given":"Hiroyuki","family":"Shimada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzuka","family":"Ataka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takami","family":"Tomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Takechi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takami","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2011,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1074069"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038%2Fnn1372"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature04533"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.3501-06.2007"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.4970-06.2007"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1515%2FREVNEURO.2009.20.1.1"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002%2Fana.21321"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.jcbfm.9600146"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2F0278-2626%2892%2990112-Y"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1444-1586.2002.00049.x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1212%2FWNL.0b013e3181af79e5"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016%2FS0197-4580%2801%2900309-8"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1001%2Farchneur.61.11.1773"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1093%2Fhmg%2F3.1.177"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1440-1789.2000.00307.x"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002%2Fana.10676"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1468-1331.2009.02757.x"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.5825-09.2010"}],"container-title":["Dementia and Geriatric Cognitive Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/330017","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/330017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:25:03Z","timestamp":1745432703000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000330017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":18,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2011,9,1]]},"published-print":{"date-parts":[[2011,9,13]]}},"URL":"https:\/\/doi.org\/10.1159\/000330017","archive":["Portico"],"relation":{},"ISSN":["1420-8008","1421-9824"],"issn-type":[{"value":"1420-8008","type":"print"},{"value":"1421-9824","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011]]}}}