Alterations of striatal dopamine receptor binding in Alzheimer disease are associated 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.


METHODS
Postmortem case control.


METHODS
Alzheimer's Disease Research Center at the University of Pittsburgh (Pa).


METHODS
Consecutive cases from the Alzheimer's Disease Research Center brain bank, neuroleptic free for at least 1 month prior to death, with neuropathologic diagnoses of AD with LB (AD + LB, n = 14), AD without LB (AD, n = 13), or normal brains (n = 8).


METHODS
Dopamine D1, D2, and D3 receptor densities, and affinities as determined by selective saturation binding studies in striatal tissue.


RESULTS
Subjects with AD + LB, compared with those with AD, demonstrated increased D1 receptor density and decreased D2 and D3 receptor density. D3 receptor density was selectively increased, however, in AD subjects with a history of psychosis, independent of the presence or absence of LB. The effect of neuroleptic treatment on D3 binding was further examined in an additional group of subjects who had received neuroleptics near the time of death. Neuroleptic treatment reduced D3 affinity with no effect on D3 density.


CONCLUSIONS
Alzheimer disease with LB is associated with selective alterations in dopamine receptor density, which may contribute to the distinct clinical profile of this group. The D3 receptor may be an important target of neuroleptic treatment of psychosis in AD.
Sweet
R A
RA
University of Pittsburgh, Division of Geriatrics and Neuropsychiatry, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213, USA. Sweetra@msx.upmc.edu
Hamilton
R L
RL
Healy
M T
MT
Wisniewski
S R
SR
Henteleff
R
R
Pollock
B G
BG
Lewis
D A
DA
DeKosky
S T
ST
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001552:Benzazepines; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D014316:Tritium
D001552:Benzazepines; C493593:DRD3 protein, human; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D014316:Tritium; C031349:7-hydroxy-2-N,N-dipropylaminotetralin