Dopamine D2 receptor bands in normal human temporal cortex are absent in Alzheimer's disease.

A modular organization of bands enriched in high concentrations of D2 receptors are observed throughout the rostral to caudal aspects of the temporal cortex of the normal human at postmortem, but are most frequently observed in the inferior and superior temporal cortices [S. Goldsmith, J.N. Joyce, Dopamine D2 receptors are organized in bands in normal human temporal cortex, Neuroscience 74 (1996) 435-451]. In the tissue derived at postmortem from Alzheimer's disease cases (AD), these D2 receptor-enriched modules were found to be largely absent at rostral and mid-levels of the temporal cortex. Regions exhibiting this loss of receptor binding also showed a marked reduction in the number of pyramidal neurons stained for D2 mRNA. In addition, the AD material exhibited numerous thioflavin-positive plaques and tangle-filled extraneuronal (ghost) pyramidal neurons that were D2 mRNA-negative. Regions that are the earliest affected and most susceptible to classical AD pathology are also most sensitive to the loss of D2 receptors. These results, along with our previous data [J.N. Joyce, C. Kaeger, H. Ryoo, S. Goldsmith, Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease, Neurosci. Lett. 154 (1993) 171-174; H. Ryoo, J. N. Joyce, The loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in Alzheimer's disease, J. Comp. Neurol. 348 (1994) 94-110], indicate that specific pathways enriched with D2 receptors, including that within modules of higher order association cortices of the temporal lobe and continued through segregated pathways within the parahippocampus and hippocampus, are particularly susceptible to the loss in AD. These dopamine D2 receptor-enriched modules may play an important role in the reciprocal activity of large groups of neurons in these high-order association cortical regions. Hence, the loss of the D2 receptor-enriched modules in Alzheimer's disease contributes to disturbances in information processing in these high-order association cortices, and may promote the cognitive and non-cognitive impairments observed in Alzheimer's disease.