The cholinergic system in the pathophysiology and treatment of Alzheimer's disease.
By Harald Hampel, M. Mesulam, A. Cuello, M. Farlow, E. Giacobini, G. Grossberg, A. Khachaturian, A. Vergallo, E. Cavedo, Peter J. Snyder and 1 more. Brain : a journal of neurology, 2018
1,488 citations recorded by the source corpus.
Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.
Subfields: Cognitive Neuroscience, Neurology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/05fde71eba9b7b770ed5b36484d7a82a6c1eb4dd
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Pharmacology
Citations in the corpus
- Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders (2021, background): “Its dysregulation is closely associated with neurodegenerative diseases such as AD [55,56].”
- Comprehensive Review on Alzheimer’s Disease: Causes and Treatment (2020, background): “As a result, the cholinergic hypothesis is based on three concepts: reduced presynaptic cholinergic markers in the cerebral cortex, severe neurodegeneration of nucleus basalis of Meynert (NBM) in the basal forebrain, which is the source of cortical cholinergic innervation, and the role of cholinergi”
- Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “100,101 Acetylcholine (ACh) is synthesized from choline and acetyl-coenzyme A by ChAT, then transported into synaptic vesicles through the vesicular acetylcholine transporter (VAChT).”