Synapses are one of the basic building blocks of the nervous system and essential for cortical communication. These building blocks are not only modifiable but also replaceable. Changes in cortical connectivity most likely underlie our ability to learn and integrate new information. We know that normal aging in the nervous system does not necessary result in a net loss of neuronal connectivity but that such loss is most likely the result of a disease process. In AD there appears to be a significant loss in many regions of the cortex and also in the hippocampus. This loss occurs even in the early stages of the disease process and may reflect the systems inability to initiate and sustain a plasticity process leading to cognitive decline106-109. The ability to attend to a stimulus and subsequently determine the merit of that stimulus requires that multiple associational areas of the cortex work in concert. The ability to store important information and to recall that information also requires that multiple regions of the brain work together. The progressive cognitive decline observed in AD most likely reflects an anatomical disruption in the cooperation of various regions of the CNS. Synapse loss in multiple association regions of the cortex is a sign of a corticocortical disconnection. The challenge is to isolate the mechanism(s) underlying this loss of connectivity early in the disease process and to mount a therapeutic regime that halts the synaptic loss and encourages synaptogenesis.
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