title: Clinical course of patients with familial early-onset Alzheimer's disease potentially lacking senile plaques bearing the E693Δ mutation in amyloid precursor protein.
abstract: OBJECTIVE
  Oligomeric amyloid β (Aβ) is currently considered to induce Alzheimer's disease (AD). We examined 2 patients with familial AD who possessed the Osaka (E693Δ) mutation in amyloid precursor protein. To the best of our knowledge, these patients are the first AD cases presumably affected with Aβ oligomers in the absence of senile plaques, and they support the Aβ oligomer hypothesis.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Familial AD patients with Osaka (E693Δ) mutation show severe dementia, cerebellar ataxia, and gait disturbances.
authors.affiliation: Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. h.shimada @ med.osaka-cu.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Suzuka
authors.initials: S
authors.lastname: Ataka
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Takechi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy; D052160:Benzothiazoles; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000209:etiology; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009483:Neuropsychological Tests; D010375:Pedigree; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D001057:Apolipoproteins E; D052160:Benzothiazoles; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18