Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology

Summary.

The biological substrate underlying the reduced cortical choline acetyltransferase (ChAT) in dementia with Lewy bodies (DLB) is incompletely understood. We compared cortical ChAT levels with Lewy body densities and neuronal loss in the nucleus basalis of Meynert (nbM) and cerebral cortex in six DLB, seven Alzheimer's disease (AD), and six control cases. We found greater neuronal loss in the nbM in DLB compared to AD (U = 9.500, p = 0.049). Mean ChAT levels in the cortex were lower in dementia patients than controls (t = 17.500, p = 0.001), and DLB cases had slightly lower ChAT levels than AD cases, but this difference was not significant (t = −0.332, p = 0.746). Overall, cortical ChAT levels correlated inversely with neuronal loss in the nbM (Spearman rank correlation coefficient = −0.53). The correlation between ChAT level and the combined factor of nbM LBs and neuronal loss was −0.59. A similar correlation between ChAT level and the combined factor of nbM neurofibrillary tangles and neuronal loss was −0.72. The correlation between ChAT and the combined factor of nbM LBs and neuronal loss was −0.81 when AD cases were excluded from the analysis. Local cortical pathology was not related to ChAT level. We conclude that neuronal loss and Lewy body formation in the nbM may contribute to the reduction in cortical ChAT in DLB.