Interplay of neurotransmitters in Alzheimer's disease 1.0.0

ChEIs are believed to target cholinergic abnormalities in Alzheimer's disease, although there is evidence indicating that their therapeutic effect may be via the glutamatergic system. NMDA receptor antagonists, in contrast, are believed to target the glutamatergic system directly PubMed:16273023

With regard to the glutamatergic system, studies suggest that ChEIs may stimulate the release of glutamate from pyramidal neurons during normal neuronal activity, while NMDA receptor antagonists are believed to block the abnormal neuronal activity that results from the presence of excess glutamate in the synapse under resting conditions. Thus, ChEIs and NMDA receptor antagonists appear to have complementary effects, as the former enhance the signals received by postsynaptic neurons during normal neurotransmission, and the latter diminish the background 'noise' that is constantly being detected by those same receptors. PubMed:16273023

The capacity for thinking and remembering is derived from various input and output pathways between the hippocampus and the neocortex,9 and all such pathways rely on signaling mediated by the neurotransmitter glutamate. PubMed:16273023

The capacity for thinking and remembering is derived from various input and output pathways between the hippocampus and the neocortex,9 and all such pathways rely on signaling mediated by the neurotransmitter glutamate. PubMed:16273023

In healthy individuals, the glutamatergic neurotransmission cycle begins in the mitochondria of hippocampal neurons, where the enzyme glutaminase catalyzes the conversion of glutamine to glutamate. Next, the vesicular glutamate transporter molecule mediates the packaging of these glutamate molecules into vesicles. Glutamate-containing vesicles are then released from the neuron, resulting in elevated synaptic concentrations of free glutamate, which can transmit neural signals by interacting with glutamatergic receptors on postsynaptic neurons PubMed:16273023