Regular Article
From Acetylcholine to Amyloid: Neurotransmitters and the Pathology of Alzheimer's Disease

https://doi.org/10.1006/neur.1996.0066Get rights and content

Abstract

Brain amyloid deposits play a central role in the histopathology of Alzheimer's disease (AD), as evidenced by increased formation of amyloid β peptides (Aβ) in genetic forms of AD that are caused by mutations in the presenilin genes, or the amyloid β protein precursor (APP) gene. Neuronal deafferentation in AD brain may also be associated with accelerated Aβ formation, because APP processing is regulated by neuronal activity, presumably via several G protein-coupled neurotransmitter receptors. Subtype-selective agonists including muscarinic m1 receptor ligands may be useful for the pharmacological reduction of Aβ formation.

References (0)

Cited by (59)

  • Ginsenosides attenuate D-galactose- and AlCl<inf>3</inf>-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease

    2016, Journal of Ethnopharmacology
    Citation Excerpt :

    Restoring the dysfunction of various neurotransmitters was a possible mechanism of the beneficial effect of ginsenosides in AD rats because the anti-AD effect of ginsenosides was proven by increasing learning and memory abilities and decreasing the damage of the hippocampus, deposition of Aβ, and expression of p-tau. AD is the most common neurodegenerative disorder that results in the failure of all but the most primitive cognitive functions, which is associated with the degeneration of many neurotransmitter systems (Nitsch, 1996). Meanwhile, in contrast to western medicine, which interacts with the human body via a single-compound drug representing a pattern of “point vs. system,” TCM interacts with the human body via a group of substances representing a pattern of “system vs. system” (Liang et al., 2008).

  • Okadaic acid induced neurotoxicity: An emerging tool to study Alzheimer's disease pathology

    2013, NeuroToxicology
    Citation Excerpt :

    Pyramidal cells are lost in the disease, subject to tangle formation, represent a major source of APP and are regulated by a neurotransmitter ACh, affected early in the disease (Francis et al., 1999). Observations in cell lines and primary neuronal cultures it is evident that the activation of muscarinic, metabotropic glutamate and other phospholipase C-linked receptors favors the non-amyloidogenic processing of APP (Nitsch, 1996). Furthermore, β-amyloid neurotoxicity is attenuated by treatment with muscarinic agonists (Emmerling et al., 1997).

  • The history of the cholinergic hypothesis

    2011, Behavioural Brain Research
    Citation Excerpt :

    These early developments of the cholinergic hypothesis had soon to confront with other ideas stemming from progress in the biochemistry of β-amyloid protein and of tau protein hyperphosphorylation, the two oldest stigmata associated with Alzheimer's disease since its early description from Alois Alzheimer [1,2] the senile plaques and the neurofibrillary tangles. These ideas gave rise to the amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease [60,61,89]. In addition to the strong biochemical evidence, genetic studies of familial cases of Alzheimer's disease played an important role of support for this hypothesis, based on the demonstration that all main mutations found in these patients were related to genes involved in the production of the precursor of β-amyloid protein or in its processing to give final fragments [6].

View all citing articles on Scopus
View full text