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

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.

Calcium, mitochondrial dysfunction and slowing the progression of Parkinson's disease

“…For example, SNc DA neurons in the rodent have axons that branch profusely in the striatum and possess as many as 200,000 vesicular release sites (Matsuda et al, 2009). Although less well characterized, neurons in the DMV, GCN, RN, LC, PPN, BFN, LH and ILN all share this feature (large, diffuse axonal projections) to varying degrees, distinguishing them from the vast majority of sensory or motor neurons in the brain, which typically have spatially focused, modestly branched axons that conform to topographic maps (Aston-Jones and Waterhouse, 2016; Baufreton et al, 2009; Hornung, 2003; Hu et al, 2015; Liu et al, 2015; Martinez-Gonzalez et al, 2011; Pfaff et al, 2012; Ratcliffe et al, 2011). Why might a long and highly branched axon increase vulnerability?…”

Cholinergic profiles in the Goettingen miniature pig (Sus scrofa domesticus) brain

“…Cholinergic neurons in the mammalian basal forebrain are found within the medial septum (MS) and vertical limb of diagonal band of Broca (VDB), the horizontal limb of diagonal band of Broca (HDB) and the magnocellular nucleus basalis of Meynert/substantia innominata complex (NBM/SI), which correspond to the Ch1, Ch2, Ch3 and Ch4 subregions, respectively (Mesulam et al, 1983b). The Ch4 complex has been subdivided into anteriomedial (Ch4am), intermediate dorsal (Ch4id) and ventral (Ch4iv), and posterior (Ch4p) subfields (Mesulam et al, 1983b; Liu et al, 2015). Ch1-2 neurons innervate the hippocampus, Ch3 the olfactory bulb and visual cortex (Mesulam et al, 1983b; Rye et al, 1984), while Ch4 neurons provide the major cholinergic innervation to the cortical mantle and amygdala (Armstrong et al, 1983; Mesulam et al, 1983b; Saper, 1984; Kasa, 1986; Eckenstein et al, 1988; Brückner et al, 1992; Semba, 2000).…”

Treatment of Dementia: Pharmacological Approaches

“…They are pharmacologically distinct and can be prescribed concurrently in patients in the moderate to severe stages of the illness. AChEIs act on inhibiting acetylcholinesterase, an enzyme directly involved in the destruction of acetylcholine leading to increasing its concentration in the nucleus basalis of Meynert in the brain and hence ameliorating the cognitive and functional aspects of AD [ 9 ]. This pharmacological category includes tacrine (Cognex) ® , donepezil (Aricept) ® , rivastigmine (Exelon) ® and galantamine (Razadyne)…”