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Parkinson's disease (PD) and Alzheimer's disease (AD) may share certain abnormalities since a subset of PD patients suffer from dementia, and some AD individuals show extrapyramidal symptoms. In vitro quantitative autoradiography was used to examine different subtypes of excitatory amino acid (EAA) receptors (NMDA, KA, and AMPA) and dopamine transporter sites in the striatum (caudate, putamen) and nucleus accumbens (NAc) from idiopathic PD, pure AD, and mixed PD/AD patients. PD and AD groups, and to a lesser extent the PD/AD groups, showed substantially increased binding to NMDA receptors in the striatum and NAc. No statistically significant changes in binding to KA and AMPA receptors were found in any patient group. 3H-mazindol binding to dopamine transporter sites was significantly decreased in the striatum and NAc of PD and PD/AD patients, but only in the putamen and NAc of AD patients. The data indicate that (1) the majority of striatal EAA receptors are not located on dopaminergic nigrostriatal nerve terminals, and (2) elevated binding to striatal NMDA receptors correlates with binding to dopamine transporter sites in PD patients, but not in AD and PD/AD individuals. Thus, the mechanisms of NMDA receptor changes in the striatum of AD and PD patients may be different. However, it is postulated that increased binding to NMDA receptors in Parkinson and Alzheimer striatum occurs in response to an insult(s) within the striatothalamocortical circuits and that this may contribute to the clinical similarities described for subsets of PD and AD patients.

Growing evidence suggests an involvement of excitatory amino acid (EAA) systems in schizophrenia. Precedent exists for changes in binding to kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, N-methyl-D-aspartate subtypes of EAA receptors. Current evidence indicates that in schizophrenia, EAA receptor levels can be decreased, unchanged, or even increased in certain brain regions and certain cases. It is likely that variability may arise from different drug histories of patients, other coexistent and undetected disease states, and the inherent heterogeneity of schizophrenia. On the other hand, it is possible that schizophrenia reflects a pattern of imbalances, not a simple unidirectional change. If so, even subtle changes may contribute significantly to the overall status of ongoing circuitry function in key brain areas implicated in schizophrenia. Together with other neurotransmitter systems, for example, dopaminergic, the net effect of EAA receptor imbalances may be greater than changes in the individual receptors and their neurotransmitters.

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