The cholinergic deficit in Alzheimer's disease: impact on cognition, behaviour and function

The International Journal of Neuropsychopharmacology
Michael S. Mega

Abstract

Although the neurodegeneration occurring in Alzheimer's disease (AD) affects multiple neurotransmitters, the cholinergic system has received the greatest attention. Acetylcholine (ACh) is fundamental to mnemonic function, assisting in the septal hippocampal pathway and facilitating cortical activation. One of the earliest pathological events in AD is the degeneration of ACh-synthesizing neurons in the subcortical nuclei of the human basal forebrain. Indeed, the loss of cholinergic function in AD is correlated with the density of histopathological markers of AD, the severity of cognitive dysfunction and disease duration. However, the precise mechanism by which the cholinergic system influences cognition, and behaviour, is unknown. Recent preliminary data from functional imaging and ligand-binding studies implicate a dynamic interaction between the nicotinic-muscarinic cholinergic receptor systems. The relatively preserved thalamic nicotinic system, compared with the dysfunctional cortical muscarinic system, may facilitate thalamocortical metabolic excitation in the failing AD brain. Thus, it is hypothesized that thalamic influence within frontal-subcortical circuits is augmented in AD patients who demonstrate a marked improvemen...Continue Reading

Citations

Jul 26, 2002·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Flavio NobiliGuido Rodriguez
Nov 18, 2003·Acta Neurologica Scandinavica·N GiladiA D Korczyn
Jul 2, 2004·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Frederick E Williams, William S Messer
Jul 10, 2003·Addiction Biology·Emmanuel Streel, Paul Verbanck
Nov 29, 2007·The Journal of Comparative Neurology·Mary Ann RaghantiChet C Sherwood
May 17, 2019·Analytical and Bioanalytical Chemistry·Marta Costas-RodríguezFrank Vanhaecke
Dec 4, 2003·Biochemical and Biophysical Research Communications·María R CastellanosAlfredo Varela

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