Soluble Aβ oligomers ultrastructurally localize to cell processes and might be related to synaptic dysfunction in Alzheimer's disease brain

Soluble Aβ oligomers have recently been considered to be responsible for cognitive dysfunction prior to senile plaque (SP) formation in Alzheimer's disease (AD) brain. To investigate the ultrastructural localization of soluble Aβ oligomers, we conducted the post-embedding immunoelectron microscopic (IEM) study using an antibody against a molecular mimic of oligomeric Aβ. We examined autopsied brains from AD patients and nondemented subjects. Oligomer-specific immunoreactions detected by IEM tended to be found with higher density (1) in AD than in nondemented brains and (2) at the axon and axon terminal in AD than in nondemented brains. These findings imply that soluble Aβ oligomers might be related to synaptic dysfunction in AD brain.