Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain

Abstract

Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

“…The hypersensitivity to scopolamine, which has been demonstrated in elderly participants when compared to younger participants (Flicker et al, 1992;Ray et al, 1992;Zemishlany and Thorne, 1991) and in participants with AD when compared to non-demented elderly participants (Sunderland et al, 1987), is consistent with the well-established age-and AD-related changes in a number of markers, including reductions in the size and number of cholinergic neurons in the NBM (McGeer et al, 1984;Whitehouse et al, 1982). Thus, the increased cognitive toxicity to trihexyphenidyl that we observed in participants with the APOE-e4 allele may reflect some form of decreased cholinergic function or reserve in this population.…”

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

“…CBF neurons of the nucleus basalis (NB) are selectively vulnerable in AD (72,73), and CBF neuron degeneration correlates with disease duration and cognitive decline (74,75). However, the molecular mechanisms(s) associated with CBF cytopathology and cellular dysfunction is unknown.…”

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

“…2,3 Following the initial report over 30 years ago, 4 a substantial literature has accumulated showing the loss of cholinergic neurons in the basal forebrain and their projections in the neocortex, hippocampus and amygdala, which results in impairment of higher cognitive functions. 5,6 At present, approved pharmacological therapies for the treatment of AD, which target this cholinergic deficit, have shown only symptomatic benefits. 7 However, not all individuals respond to cholinesterase inhibitor (ChEI) treatment.…”