Amyloid deposition in the nucleus basalis of Meynert complex: a topographic marker for degenerating cell clusters in Alzheimer's disease

Abstract

The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuro-pathologically characterised by the appearance of three intracerebral formes of twisted beta-pleated sheet (amyloid) fibrils, neurofibrillary tangles, amyloid-containing neuritic plaques and congophilic amyloid angiopathy. In the present study the quantitative relationship between these hallmarks of the disease, amyloid deposition and neuronal loss in the cholinergic basal forebrain system, was investigated in ten cases of Alzheimer's disease. Besides a constant involvement of the cerebral cortex and hippocampus, all cases of Alzheimer's disease show a large amount of amyloid in the medial septal nucleus, in the diagonal band nucleus and in the substantia innominata which is correlated with neuronal loss in these areas. These amyloid deposits in the basal forebrain are due to congophilic angiopathy associated with plaques and neurofibrillary tangles. The distribution of amyloid deposition in the basal forebrain is restricted entirely to those neuronal clusters which represent the origin of cholinergic innervation of the cerebral cortex and hippocampus. Immediately adjacent structures are not affected. These findings suggest a pathogenetic role of amyloid deposition in the mechanism of degeneration of the cholinergic basal forebrain system.

Galanin Fiber Hypertrophy within the Cholinergic Nucleus Basalis during the Progression of Alzheimer’s Disease

“…Transgenic mice that overexpress amyloid-plaque-like deposits in the hippocampus and entorhinal cortex exhibit an increase in GAL fi ber density in these areas [56,58] . Therefore, amyloid deposition, which becomes prominent within the cholinergic NB and its cortical projection sites during late-stage AD [59] , may also play a role in triggering the GAL plasticity response.…”

Galanin – 25 years with a multitalented neuropeptide

“…Since neuron loss was not evident at this age [63,64], these observations suggest that GAL is triggered by amyloidosis-related neurotoxicity rather than frank neurodegeneration in transgenic animal models of AD. Whether amyloid plaque deposition, which is prominent in vulnerable cognitive brain regions in AD [65,66], also triggers GAL overexpression in these areas in the human condition remains an open question. Neurofibrillary tangles (NFTs), filamentous deposits composed of aggregated tau microtubule-binding proteins [67,68], are also a cardinal neuropathological feature of AD.…”

Phases of Aβ-deposition in the human brain and its relevance for the development of AD

“…11 Outside the MTL, A␤-deposits are seen in all parts of the allo-and neocortex, in the striatum, the hypothalamus, the thalamus, the basal forebrain nuclei, the cerebellum, and in several brainstem nuclei. 1,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] At this point, it is not known whether ␤-amyloidosis outside the MTL expands in a hierarchical manner as well, whether in clinically proven AD cases it represents a later stage of ␤-amyloidosis seen in nondemented patients with AD-related neuropathology, or whether ␤-amyloidosis in AD is substantially different from A␤-deposition in nondemented individuals.…”

“…6,32 Immunohistochemistry. In paraffin and PEG sections, the presence of A␤ was observed with an antibody directed against A␤ [17][18][19][20][21][22][23][24] (4G8, Signet [Dedham, MA], 1/5000, 48 hours at 4°C) after formic acid pretreatment. The primary antibody was detected with a biotinylated secondary antibody and the ABC complex, and visualized with 3,3-diaminobenzidine (DAB).…”