Absence of synaptophysin near cortical neurons containing oligomer Abeta in Alzheimer's disease brain.

Soluble amyloid beta protein (Abeta) oligomers have been considered recently to be responsible for the cognitive dysfunction that sets in prior to senile plaque formation in the Alzheimer's disease (AD) brain. By using the newly prepared antibody against oligomer Abeta, rather than fibrillar or monomer Abeta, we observed that oligomer Abeta in AD brains was localized as clusters ofdot-likeimmunostains in the neurons in a manner different from that in senile plaques. The relationship of oligomer Abeta with synaptophysin, a synaptic molecular marker, was examined because oligomer Abeta is widely believed to be related to synaptic failure. We observed that immunostainings for synaptophysin were absent near neurons bearing clusters of oligomer Abeta. The present study provides morphological evidence to support the idea that accumulated oligomer Abeta, but not fibrillar Abeta, is closely associated with synaptic failure, which is the major cause of cognitive dysfunction.