Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain

Among the neurotransmitter abnormalities that have been investigated in Alzheimer's disease (AD), deficits in the cholinergic system have been the most intensively studied. Another key neurotransmitter system involved with emotion and cognition is the dopaminergic system. Here we have investigated alterations in all five dopamine receptor subtypes in AD brain. Using antipeptide rabbit antibodies for each of the five dopamine receptors (D1-D5) we mapped the distribution of these receptors in postmortem AD and age-matched control brains in the frontal cortex, utilizing biotin-avidin immunocytochemistry. All five DR subtypes were expressed as cell surface and cytoplasmic proteins. Receptor-specific changes in control and AD brain were identified as follows: D4R and D3R were the predominant receptor subtypes in age-matched controls followed by D2R and D1R; D5R is the least expressed receptor subtype. In AD brain, D2R and D5R are well expressed in comparison to D1R, D3R and D4R. Expression of D1R, D3R and D4R was severely reduced in AD cortex. D2R expression is moderately reduced in the frontal cortex of AD brain. D5R is the only receptor subtype whose expression is increased in AD frontal cortex. Furthermore, in AD, we found comparable expression of D3R in astrocytes, whereas D5R-like immunoreactivity is significantly increased in astrocytes, in comparison to normal frontal cortex, where it was predominantly neuronal. These results demonstrate subtype-specific changes in dopamine receptors in AD that may be important in disease pathophysiology and that may also serve as potential targets for therapeutic intervention in AD.