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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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
Volume32
Issue number1
DOIs
Publication statusPublished - 01-09-2011

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Amyloid beta-Protein Precursor
Amyloid Plaques
Alzheimer Disease
Mutation
Positron-Emission Tomography
Amyloid
Gait Ataxia
Magnetic Resonance Imaging
Cerebellar Ataxia
Atrophy
Cerebrospinal Fluid
Dementia
Biomarkers
Brain

All Science Journal Classification (ASJC) codes

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

Cite this

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abstract = "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.",
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Clinical course of patients with familial early-onset Alzheimer's disease potentially lacking senile plaques bearing the E693Δ mutation in amyloid precursor protein. / Shimada, Hiroyuki; Ataka, Suzuka; Tomiyama, Takami; Takechi, Hajime; Mori, Hiroshi; Miki, Takami.

In: Dementia and Geriatric Cognitive Disorders, Vol. 32, No. 1, 01.09.2011, p. 45-54.

Research output: Contribution to journalArticle

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AU - Mori, Hiroshi

AU - Miki, Takami

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