Basic Science and Pathogenesis.

Background: The failure of amyloid plaque-reducing drugs to reverse cognitive decline in Alzheimer's disease (AD) has suggested that treatments might be more effective in early or prodromal stages of the disease. However, the progression of synaptic and circuit changes associated with Aβ overexpression, particularly at very early ages, have not been well-characterized. Indeed, evidence from both human and animal studies indicates that brain structure and function might be altered months to years before plaques can be detected.

Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.

The limited success of plaque-reducing therapies in Alzheimer's disease suggests that early treatment might be more effective in delaying or reversing memory impairments. Toward this end, it is important to establish the progression of synaptic and circuit changes before onset of plaques or cognitive deficits. Here, we used quantitative, fluorescence-based methods for synapse detection in CA1 pyramidal neurons to investigate the interaction between abnormal circuit activity, measured by Fos-immunoreactivity, and synapse reorganization in mouse models of amyloidosis.