Amyloid β Protein Modulates Glutamate-Mediated Neurotransmission in the Rat Basal Forebrain: Involvement of Presynaptic Neuronal Nicotinic Acetylcholine and Metabotropic Glutamate Receptors

Amyloid beta mediates memory formation

“…Hence, similar behavioral outcomes are evoked by hippocampal treatments that block the function of either endogenous Ab or nAchRs, suggesting, in agreement with previous literature (Chin et al 2007), that Ab(1-42) might exert its modulatory function on memory formation via interaction with nAchRs.…”

Impact of Sustained Exposure to β-Amyloid on Calcium Homeostasis and Neuronal Integrity in Model Nerve Cell System Expressing α4β2 Nicotinic Acetylcholine Receptors

“…This would, in turn, implicate A␤ in activity-coupled synaptic regulation through target receptors. In the absence of AD, A␤ appears to be present in the high picomolar range (7) and previous work has demonstrated a direct agonist-like action of soluble picomolar-nanomolar A␤ via nAChRs at presynaptic sites (12,15,37,45,46). Acute picomolar A␤ was also found to enhance synaptic plasticity in a nAChR-dependent fashion (3,4).…”

Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

“…135 Second, amyloid β can activate α 7 nicotinic receptors or NMDA receptors and increase Ca 2+ entry into the cell. This • Increase long-term depression 98,[108][109][110] • Decrease synaptic density and alter the morphology of dendritic spines 98,106,107,115 • Regulate glutamate uptake from the synapse 60,73,110,116,117 • Stimulate release of glutamate 117,118 • Increase endocytosis of AMPA and NMDA receptors 108,119 • Disrupt the postsynaptic density and prevent NMDA and AMPA receptors reaching the cell surface 120,121 • Increase tau phosphorylation/cell death [122][123][124][125][126] AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA = N-methyl-D-aspartate.…”

“…25,84,159 Studies on a variety of cell lines and primary cultured neurons suggest that amyloid β toxicity might be mediated either by interaction with a hydroxysteroid dehydrogenase enzyme or by plasma membrane receptors for advanced glycation end products, class A scavenger receptor, p75 neurotrophin receptor, amylin or α 7 nicotinic receptors. 117,[160][161][162][163][164] However, a number of studies have clearly indicated that amyloid β toxicity is mediated, at least in part, by glutamate-mediated excitotoxicity, which involves activation of the NMDA receptors, leading to elevated intracellular Ca 2+ and consequent stimulation of a cascade of enzymes resulting in cell death. 28,76,77,158 Amyloid β-induced excitotoxic cell death was first reported in the early 1990s, with initial reports indicating that prolonged exposure of amyloid β peptides, including amyloid β25-35 and amyloid β1-38 with glutamate induced greater cell death than exposure to amyloid β or glutamate alone in mouse cortical neuronal cultures.…”

“…Antagonists of NMDA and AMPA receptors can prevent influx of Ca 2+ and cell death. 27 Alternatively, it is possible that amyloid β-related peptides can increase extracellular glutamate levels by potentiating release 117,118,155 and/or inhibiting the uptake of the neurotransmitter, 116,153 which can subsequently trigger death of neurons by excitotoxicity. It is therefore likely that a combination of reduced glutamate clearance from the synaptic cleft, increased release of glutamate from neurons and glia, and the subsequent activation of the glutamate receptors contribute to toxicity mediated by amyloid β-related peptides.…”