Abstract
Cholinergic neurotransmission is essential for cognitive processes in the human brain and was found to be disturbed in Alzheimer’s disease. Since Alzheimer’s disease is associated with a decline in cognitive abilities, a fist causal relationship—disturbed cholinergic transmission and memory loss—was found. Subsequently, a solid pathogenetic perspective explaining Alzheimer’s dementia was formulated: the cholinergic hypothesis of Alzheimer’s disease. The premise of a cholinergic disturbance was the starting point of the development of a pharmaceutical interventional concept resulting in a first generation of Alzheimer’s drugs, the so-called acetylcholinesterase (AChE) inhibitors. Loss of cholinergic neurotransmission was compensated at the level of neurochemistry.
With the approval of the compound tacrine in the United States in 1991, the first Alzheimer’s disease drug was approved. While this was certainly a seminal step forward in Alzheimer’s research, later it was discovered that clinically AChE inhibitors can mitigate some disease symptoms but cannot stop the degeneration of neurons or even halt the disease. To date, the three AChE inhibitors donepezil, galantamine, and rivastigmine are still approved for Alzheimer’s therapy in the United States. While the disease was acknowledged as an acetylcholine deficiency syndrome, there was little progress regarding the initial trigger of the pathological events.
Around the same time (in the late 1970s), a short editorial by Robert Katzman significantly impacted the Alzheimer’s field by proposing to combine the senile and the presenile forms of the disease to one etiopathologic entity. From today’s view, this editorial was highly influential, indeed, and changed the flow of Alzheimer’s research.
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Behl, C. (2023). Focus on Neurochemistry Led to the Cholinergic Hypothesis of Alzheimer’s Disease. In: Alzheimer’s Disease Research. Springer, Cham. https://doi.org/10.1007/978-3-031-31570-1_5
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