Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease.

Alan King Lun Liu,Steve M Gentleman,Raymond Chuen-Chung Chang,Ronald K B Pearce

doi:10.1007/s00401-015-1392-5

Abstract

It has been well established that neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer’s disease (AD). Friedrich Lewy first observed his eponymous inclusion bodies in the nbM of postmortem brain tissue from patients with Parkinson’s disease (PD) and cell loss in this area can be at least as extensive as that seen in AD. There has been confusion with regard to the terminology and exact localisation of the nbM within the human basal forebrain for decades due to the diffuse and broad structure of this “nucleus”. Also, while topographical projections from the nbM have been mapped out in subhuman primates, no direct clinicopathological correlations between subregional nbM and cortical pathology and specific cognitive profile decline have been performed in human tissue. Here, we review the evolution of the term nbM and the importance of standardised nbM sampling for neuropathological studies. Extensive review of the literature suggests that there is a caudorostral pattern of neuronal loss within the nbM in AD brains. However, the findings in PD are less clear due to the limited number of studies performed. Given the differing neuropsychiatric and cognitive deficits in Lewy body-associated dementias (PD dementia and dementia with Lewy bodies) as compared to AD, we hypothesise that a different pattern of neuronal loss will be found in the nbM of Lewy body disease brains. Understanding the functional significance of the subregions of the nbM could prove important in elucidating the pathogenesis of dementia in PD.

Highlights

The identification of Lewy bodies (LB) and neuronal loss in the substantia nigra is considered the gold standard for the neuropathological diagnosis of Parkinson’s disease (PD), these two pathological features were first recognised by Friedrich Lewy in the nucleus basalis of Meynert in 1913
In earlier studies, no distinction was made between PD with dementia (PDD) and dementia with Lewy bodies (DLB) [79, 80], as DLB is a more recently established clinical entity [66], and it would be of interest to investigate whether the pattern of cell loss within the nucleus basalis of Meynert (nbM) subregions differs in PDD and DLB
Following our literature review on the studies of the nbM above, we revisited the original work by Friedrich Lewy [30] and found that the area he defined as the nbM was from the optic tract to septum pellucidum

Summary

Introduction

The identification of Lewy bodies (LB) and neuronal loss in the substantia nigra is considered the gold standard for the neuropathological diagnosis of Parkinson’s disease (PD), these two pathological features were first recognised by Friedrich Lewy in the nucleus basalis of Meynert (nbM) in 1913. Using the aforementioned guideline to divide the nbM into the anterior, intermediate and posterior subdivisions, we identified the regional susceptibility to neuronal loss in AD (Table 3). Doucette and colleagues reported that in moderate AD, the anterior nbM had a 50 % neuronal loss while the decrease in cell number was not significant in intermediate and posterior nbM [25].

Results

Conclusion