SELECTIVE INCREASE OF NMDA-SENSITIVE GLUTAMATE BINDING IN THE STRIATUM OF PARKINSONS-DISEASE, ALZHEIMERS-DISEASE, AND MIXED PARKINSONS-DISEASE ALZHEIMERS-DISEASE PATIENTS - AN AUTORADIOGRAPHIC STUDY

Parkinson's disease (PD) and Alzheimer's disease (AD) may share certai n abnormalities since a subset of PD patients suffer from dementia, an d some AD individuals show extrapyramidal symptoms. In vitro quantitat ive autoradiography was used to examine different subtypes of excitato ry amino acid (EAA) receptors (NMDA, KA, and AMPA) and dopamine transp orter 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 group, showed substantially i ncreased binding to NMDA receptors in the striatum and NAc. No statist ically significant changes in binding to KA and AMPA receptors were fo und in any patient group. H-3-mazindol binding to dopamine transporter sites was significantly decreased in the striatum and NAc of PD and P D/AD patients, but only in the putamen and NAc of AD patients. The dat a indicate that (1) the majority of striatal EAA receptors are not loc ated on dopaminergic nigrostriatal nerve terminals, and (2) elevated b inding 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 a nd PD patients may be different. However, it is postulated that increa sed binding to NMDA receptors in Parkinson and Alzheimer striatum occu rs in response to an insult(s) within the striatothalamocortical circu its and that this may contribute to the clinical similarities describe d for subsets of PD and AD patients.