Decreased brain dopaminergic transporters in HIV-associated dementia patients.
HIV has a propensity to invade subcortical regions of the brain, which may lead to a subcortical dementia termed HIV-cognitive motor complex. Therefore, we aimed to assess whether dopamine (DA) D2 receptors and transporters (DAT) are affected in the basal ganglia of subjects with HIV, and how these changes relate to dementia status. Fifteen HIV subjects (age 44.5 +/- 11 years; CD4 185 +/- 130/mm3)) and 13 seronegative controls (42 +/- 12 years) were evaluated with PET to assess availability of DAT ([11C]cocaine) and DA D2 receptor ([11C]raclopride). HIV patients with associated dementia (HAD), but not those without dementia (ND) had significantly lower DAT availability in putamen (-19.3%, P = 0.009) and ventral striatum (-13.6%, P = 0.03) compared with seronegative controls. Higher plasma viral load in the HIV dementia patients correlated with lower DAT in the caudate (r = -0.7, P = 0.02) and putamen (r = -0.69, P = 0.03). DA D2 receptor availability, however, showed mild and non-significant decreases in HIV patients. These results provide the first evidence of DA terminal injury in HIV dementia patients, and suggest that decreased DAT may contribute to the pathogenesis of HIV dementia. The greater DAT decrease in the putamen than in the caudate parallels that observed in Parkinson's disease. The inverse relationship between viral burden and DAT availability further supports HIV-mediated neurotoxicity to dopaminergic terminals.
Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY, USA.
Gene-Jack
GJ
Wang
Linda
L
Chang
Nora D
ND
Volkow
Frank
F
Telang
Jean
J
Logan
Thomas
T
Ernst
Joanna S
JS
Fowler
D015526:AIDS Dementia Complex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000821:virology; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006678:HIV / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D012367:RNA, Viral / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D019562:Viral Load
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012367:RNA, Viral; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human