DAMAGE TO DOPAMINE SYSTEMS DIFFERS BETWEEN PARKINSONS-DISEASE AND ALZHEIMERS-DISEASE WITH PARKINSONISM

Parkinsonism occurs in approximately 35 to 40% of patients with Alzhei mer's disease (AD) even with little or no neuronal degeneration in the substantia nigra, which in idiopathic Parkinson's disease (PD) result s in the severe loss of striatal dopamine transporter sites. It is not known if there is a loss of striatal dopamine transporter sites in AD with coexistent parkinsonism (AD/parkinsonism). We quantified the pat tern of these sites in the striatum and midbrain of patients with the clinical diagnosis of PD, AD, and AD/parkinsonism in comparison with a group of age-matched control subjects. We also quantified the number of D2 receptors and the levels of tyrosine hydroxylase in the substant ia nigra and ventral tegmental area of the same groups. The results sh owed that in AD the loss of dopamine transporter sites was restricted to the nucleus accumbens. The loss of these sites in the AD/parkinsoni sm group was more extensive than in the AD group, with the most severe losses in the rostral caudate and putamen and least in the caudal cau date and putamen. While the PD group showed an equally severe reductio n in numbers of sites, the caudal to rostral gradient of loss differed from that in the AD/parkinsonism group. The PD group also showed a ma rked loss of dopamine transporter sites, tyrosine hydroxylase, and D2 autoreceptors (located on dopamine neurons) in the substantia nigra an d ventral tegmental area. In contrast, no reductions in dopamine trans porter sites, tyrosine hydroxylase, and D2 autoreceptors were observed in the substantia nigra and ventral tegmental area of the AD or AD/pa rkinsonism groups. Thus, the loss of striatal dopamine transporter sit es in AD/parkinsonism may be related to the clinical parkinsonian symp toms. However, the loss is not simply the result of neuronal degenerat ion in the substantia nigra, but must derive from other processes.