Neuroreceptor changes in Alzheimer disease.
Multiple neuroreceptor changes are present in Alzheimer disease. These observations are based upon analysis from autopsy brain tissue or more seldom from neurosurgical biopsies. The drawback of information from autopsy material is that the receptor changes represent the final stage of the dementia disorder. It might therefore be somewhat misleading to base therapeutic strategies on these findings. Hopefully, new imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) will provide valuable new in vivo data from the earlier course of the disease. Among the transmitter systems changed in Alzheimer disease, the cholinergic system shows the most consistent deficits. Cholinergic muscarinic receptors seem to be preserved in Alzheimer brains while nicotinic receptors show losses. The number of serotonin (both 5-HT1 and 5-HT2) and glutamate receptors are also reduced. Interestingly, kainate receptors increase in number while NMDA receptors are reduced in cortical Alzheimer tissue. Common for all receptor changes in Alzheimer disease is that the changes in number of binding sites are seen while the affinity constant remains unchanged. alpha- and beta-receptors and dopamine receptors are relatively preserved in Alzheimer brains. Among the neuropeptides, losses in receptor sites have been reported for somatostatin and neuropeptide Y (NPY). Interestingly, the number of CRF receptors are increased in cortical areas of Alzheimer brains. Thus, the muscarinic (M1), kainate, and CRF receptors show receptor compensatory reactions probably due to degenerative reactions in Alzheimer disease. Few attempts have been made to visualize neuroreceptors in vivo in Alzheimer patients. The field, however, is in dynamic progress. Reduced numbers of nicotinic receptors have been visualized in the brain of Alzheimer patients by PET and [11C]-nicotine and confirm earlier observations in post-mortem brain tissues. A lower uptake of (R)(+)[11C]nicotine compared to (S)(-)[11C]nicotine in patients with a mild form of dementia might be a possible diagnostic marker. SPECT studies indicate preserved muscarinic receptors in Alzheimer brains. Analysis of neuroreceptor changes in peripheral nonneural tissues have shown a reduction in nicotinic and muscarinic receptors in peripheral lymphocytes obtained from Alzheimer patients.
Nordberg
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Department of Pharmacology, Uppsala University, Sweden.
D000544:Alzheimer Disease / Q000503:physiopathology*; D006801:Humans; D011984:Sensory Receptor Cells / Q000502:physiology*