Comparative anatomic data suggest that a telencephalic system of brain regions underwent selective expansion during primate evolution, including the neocortex and connected non-neocortical regions such as posterior hippocampus and amygdala. Molecular changes during evolution likely made this system vulnerable to the neurodegeneration of Alzheimer's disease, as neuropathological and functional imaging studies using positron emission tomography (PET) show that the affected regions become abnormal earlier and more extensively in disease than do non-system regions. Functional changes occur at the level of the synapse in these regions. Accordingly, a model and method using activation brain blood flow studies with PET in individual subjects was designed to examine synaptic integrity in vivo, and to see how synaptic failure can be reversed with modulatory drugs during cognitive or psychophysical activation of the affected regions. The affected regions also demonstrate a reduced critical temperature of membrane lipids, hypothesized to cause membrane instability and ascribed to reduced concentrations of phosphatidylethanolamine.
