Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease

The brains of Alzheimer's disease patients contain extracellular A beta amyloid deposits (senile plaques). Although genetic evidence causally links A beta deposition to the disease, the mechanism by which A beta disrupts cortical function is unknown. Using triple immunofluorescent confocal microscopy and three-dimensional reconstructions, we found that neuronal processes that cross through an A beta deposit are likely to have a radically changed morphology, We modeled the electrophysiological effect of this changed morphology and found a predicted delay of several milliseconds over an average plaque. We propose that this type of delay, played out among thousands of plaques throughout neocortical areas, disrupts the precise temporal firing patterns of action potentials, contributing directly to neural system failure and dementia.