Dementia Japan 24: 37-45, 2010

The Aβ oligomer hypothesis:A new view of the pathogenesis of Alzheimer's disease

Takami Tomiyama

Department of Neuroscience, Osaka City University Graduate School of Medicine

    Alzheimer's disease is currently believed to begin with synaptic dysfunction caused by soluble oligomers of Aβ.  This view, termed oligomer hypothesis, is based primarily on experimental evidence that Aβ oligomers, including low-n oligomers such as dimers and trimers, 12-mers termed ADDLs or Aβ^*56, and larger protofibrils, impair synaptic plasticity and memory and cause synapse loss when applied exogenously in vivo and in vitro.  Our finding that APP E693Δ mutation causes disease by enhancing Aβ oligomerization without forming Aβ fibrils or senile plaques provides genetic validation in humans of this hypothesis.  The oligomer hypothesis would bring new strategies of diagnoses and treatments for Alzheimer's disease.

Address correspondence to Dr. Takami Tomiyama, Department of Neuroscience, Osaka City University Graduate School of Medicine (1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan)