Some cholinergic themes related to Alzheimer's disease: Synaptology of the nucleus basalis, location of m2 receptors, interactions with amyloid metabolism, and perturbations of cortical plasticity

Cholinergic neurons in the nucleus basalis of Meynert (nbM) receive cholinergic, GABAergic and monoaminergic synapses. Only few of these neurons display the sort of intense m2 immunoreactivity that would be expected if they were expressing m2 as their presynaptic autoreceptor. The depletion of cortical m2 in Alzheimer's disease (AD) appears to reflect the loss of presynaptic autoreceptors located on incoming axons from the nucleus basalis of Meynert (nbM) and also the loss of postsynaptic receptors located on a novel group of nitric oxide producing interstitial neurons in the cerebral cortex. The defect of cholinergic transmission in AD may enhance the neurotoxicity of amyloid beta, leading to a vicious cycle which can potentially accelerate the pathological process. Because acetylcholine plays a critical role in regulating axonal growth and synaptic remodeling, the cholinergic loss in AD can perturb cortical plasticity so as to undermine the already fragile compensatory reserve of the aging cerebral cortex.

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