Clinical course of patients with familial early-onset Alzheimer's disease potentially lacking senile plaques bearing the E693Δ mutation in amyloid precursor protein

Hiroyuki Shimada, Suzuka Ataka, Takami Tomiyama, Hajime Takechi, Hiroshi Mori, Takami Miki

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Background/Aims: 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.

Original languageEnglish
Pages (from-to)45-54
Number of pages10
JournalDementia and Geriatric Cognitive Disorders
Issue number1
Publication statusPublished - 01-09-2011


All Science Journal Classification (ASJC) codes

  • Geriatrics and Gerontology
  • Cognitive Neuroscience
  • Psychiatry and Mental health

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