CHOLINE-ACETYLTRANSFERASE MESSENGER-RNA EXPRESSION IN THE STRIATAL NEURONS OF PATIENTS WITH ALZHEIMERS-DISEASE

Besides cortical pathology, Alzheimer's disease (AD) is associated wit h a massive loss of cholinergic neurons in the basal forebrain. The re sulting cortical cholinergic depletion is thought to contribute to the major cognitive impairment described in AD. A selective loss of choli nergic neurons has also been observed in the ventral striatum, despite the lack of any major neurochemical dysfunction in the striatum of pa tients with AD. To examine possible changes in the functional activity of the neurons that remain in the striatum of AD patients, the expres sion level of the gene coding for choline acetyltransferase (ChAT) was evaluated using in situ hybridization in the caudate nucleus, putamen and ventral striatum. Quantitative analysis showed (i) a marked decre ase in the number of ChAT mRNA-positive neurons in the ventral striatu m, and (ii) significantly reduced ChAT mRNA expression in the survivin g cholinergic neurons of the ventral striatum, whereas it was only sli ghtly decreased in those of the dorsal striatum. Our data support the hypothesis of a down-regulated expression of ChAT in striatal choliner gic neurons, especially in those most vulnerable to the neurodegenerat ive process. The subnormal ChAT mRNA content may be the consequence of changes in the level of transcription of the ChAT gene, possibly in r elation to sustained suffering still present at the late stages of thi s disease. Furthermore, the involvement of the ventral striatum in Alz heimer's disease may account for some of the behavioral and motor dysf unctions often observed in patients with AD. (C) 1997 Elsevier Science Ireland Ltd.