Alterations of striatal dopamine receptor binding in Alzheimer disease areassociated with Lewy body pathology and antemortem psychosis

Background: Lewy bodies (LB) are present in at least 20% to 30% of persons with Alzheimer disease (AD) and contribute to the risk of psychosis and to excess cognitive burden. Objective: To determine whether altered striatal dopamine receptor binding is associated with LB and psychosis in AD. Design: Postmortem case control. Setting: Alzheimer's Disease Research Center at the University of Pittsburg h (Pa). Participants: Consecutive cases from the Alzheimer's Disease Research Cente r brain bank, neuroleptic free for at least 1 month prior to death, with ne uropathologic diagnoses of AD with LB (AD + LB, n = 14), AD without LB (AD, n = 13), or normal brains (n = 8). Main Outcome Measures: Dopamine D-1, D-2, and D-3 receptor densities, and a ffinities as determined by selective saturation binding studies in striatal tissue. Results: Subjects with AD + LB, compared with those with AD, demonstrated i ncreased Di receptor density and decreased D-2 and D-3 receptor density. D- 3 receptor density was selectively increased, however, in AD subjects with a history of psychosis, independent of the presence or absence of LB. The e ffect of neuroleptic treatment on D-3 binding was further examined in an ad ditional group of subjects who had received neuroleptics near the time of d eath. Neuroleptic treatment reduced D-3 affinity with no effect on D-3 dens ity. Conclusions: Alzheimer disease with LB is associated with selective alterat ions in dopamine receptor density, which may contribute to the distinct cli nical profile of this group. The D-3 receptor may be an important target of neuroleptic treatment of psychosis in AD.