Sub-regional nucleus basalis of Meynert pathology in Lewy body disorders

Abstract

INTRODUCTION: Cortical acetylcholine is essential for normal cognitive functioning and its innervation originates from the nucleus basalis of Meynert (nbM). Retrograde tracer studies on non-human primates have shown a topographic innervation from different sub-regions of the nbM with the anterior portion providing afferents to the frontal and medial cortical regions; intermediate nbM to the lateral cortical regions; and posterior division innervating the temporal polar region. In Alzheimer’s disease (AD), the posterior nbM has shown the greatest degree of neuronal loss. However, detailed sub-regional analysis of the nbM has not been performed on Lewy body disorders (LBD). With functional imaging studies highlighting the difference in cortical cholinergic deficits between AD and LBD, we hypothesise a differential susceptibility to pathology in LBD. MATERIAL AND METHODS: Basal forebrain tissues from 43 Parkinson’s disease (PD). 20 PD with mild cognitive impairment (PD-MCI), 61 PD with dementia (PDD), 8 Dementia with Lewy Bodies (DLB) and 9 age-matched controls were obtained from the Parkinson’s UK Tissue Bank. Tissues were stained with H&E for the determi- nation of nbM sub-regions, and immunohistochemistry, with choline acetyltransferase (ChAT) antibodies, for the quantification of cholinergic neurons. RESULTS: A graded decrease of ChAT-positive neuronal density was observed as PD cognitive disability increased. In PDD, all nbM sub-regions appeared to be equally affected, whereas the degree of neuronal loss in PD without cognitive deficit was most severe in the posterior nbM sub-region. No significant difference between sub-regional cell loss in PDD and DLB was observed. CONCLUSION: Our results show that sub-regional pathology exists in different LBD. Further work is now needed to determine if this corresponds to the findings from recent functional imaging studies.