Loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in alzheimer's disease

Abstract

The anatomy of the hippocampus, including the organization of its intrinsic neural circuits and afferents, is organized along a rostrocaudal axis. Dopamine D2 receptors are expressed in specific regions of the hippocampal complex (hippocampal subfields, entorhinal cortex, perirhinal cortex) and show differential expression along this axis. The dentate gyrus and CA3/CA4 subfields show higher numbers of D2 receptors in the rostral than in the caudal levels. In contrast, the subiculum shows the reverse gradient. We report here that Alzheimer's disease (AD) is associated with reduced expression of the dopamine D2 receptor, but the effects differ with respect to the rostrocaudal axis and area within the hippocampal complex. The number of D2 receptors is significantly reduced in the molecular layer of the dentate gyrus, CA3 subfield, and subiculum. For the dentate gyrus and subiculum, there were greater losses at more rostral levels. The CA3/CA4 subfields showed the greatest losses caudally. The entorhinal cortex, which shows only modest expression of D2 receptors in controls, does not exhibit reduced numbers in AD. The external laminae of the rostral perirhinal cortex showed more significant losses than more caudally in this cortical field. The regions showing loss of D2 receptors do not typically contain neuritic plaques, neurofibrillary tangles, or significant neuron loss. Thus other mechanisms must account for the unique gradient of D2 receptor loss in the hippocampus. The regions of reduced expression of dopamine D2 receptors do correlate well with the terminal zone of the dentate association pathway, the afferents from the amygdala and perirhinal cortex, and the sources of those afferents within the amygdala and perirhinal cortex. The specific patterns of reduced D2 receptor expression in AD are likely to contribute significantly to the disrupted information flow into and out of the hippocampus and, thus, of functions subserved by this system.