Differential pattern of neuronal loss in the cholinergic basal forebrain in Lewy body disorders

Abstract

INTRODUCTION: The basal forebrain cholinergic system consists of the medial septum/diagonal band nucleus (MS/DBN), nucleus basalis of Meynert (nbM) and nucleus subputaminalis (NSP). These nuclei project to the hippocampus and various cortical regions. A posterior-anterior gradient of cortical cholinergic deficit in Lewy body disorders (LBD) has been reported on imaging studies. However, it is not clear whether this pattern is reflected by the neuronal loss in various basal forebrain cholinergic nuclei. OBJECTIVES: To characterise the pattern of neuronal loss in different subdivisions of the cholinergic basal forebrain in Lewy body disorders. METHODS: Tissue sections containing the basal forebrain from 93 PD, 100 PDD, 14 DLB and 15 age-matched controls were stained using immunohistochemistry with choline acetyltransferase (ChAT) antibodies. ChAT-positive neurons in the MS/DB, NSP and nbM were quantified, blind to the clinical diagnosis. Results: A significant reduction of ChAT-positive neurons was found in LBD cases, with demented cases showing a greater loss. All subdivisions of the nbM were equally affected in PDD whereas the anterior and posterior nbM have a greater loss in PD. DLB cases have a significantly lower number of ChAT-positive neurons in the MS/DBN. A trend of decrease in ChAT-positive neurons was observed in the NSP among LBD cases. CONCLUSIONS: We have identified a differential pattern of cell loss in various subdivisions of the cholinergic basal forebrain in LBD cases. This could possibly explain the specific cognitive profile presented by LBD patients and support findings from recent imaging studies.