The interplay of neurotransmitters in Alzheimer's disease
Abstract
Evidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-D-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.
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Overstimulation of NMDA receptors by glutamate can induce neuronal injury owing to excitotoxicity in some cases.
“Overstimulation of NMDA receptors by glutamate, on the other hand, can induce neuronal injury owing to excitotoxicity in some cases (Francis, 2005).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Francis, 2005
A couple of memory-related processes could potentially be modulated by Bacopa monnieri in isolation or in combination with other compounds.
“Although memory is greatly affected by a plethora of factors, such as hormones, cyclic AMP, neurotransmitters, focus, attention, synapse formation, nutrients, and protein transcription, a couple of these processes could potentially be modulated by B. monnieri in isolation or in combination with other compounds as partially shown in these studies [56,57,101,110,111].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [110]
Increasing acetylcholine concentration at the synapse by inhibiting AChE is one approach to slow down the progression of AD.
“An increase of acetylcholine concentration (ACh) at the synapse by inhibiting the acetylcholinesterase (AChE) is one of the approaches to slow down the progression of AD [18,19,20,21,22,23,24,25,26].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [26]
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- Authors
- Francis, P. T.
- Affiliations
- King's College London (GB)
- Corresponding author
- Francis, Paul T.
- ORCID
- Francis, Paul T.
- Venue
- CNS Spectrums
- Publisher
- Cambridge University Press (CUP)
- Published
- 2005-11
- Volume
- 10
- Issue
- S18
- Pages
- 6-9
- ISSN
- 1092-8529 (ISSN-L)
- 2165-6509
- OpenAlex
- W1682771183
- Semantic Scholar
- fb1cc019d132438bbc258437854ec92d9016d09d
- Cited by
- 302
- References
- 16
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 28 · 2023: 42 · 2022: 35 · 2021: 29 · 2020: 22 · 2019: 26 · 2018: 26 · 2017: 8 · 2016: 6 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 3
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Spectrums (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, acetylcholine, glutamate, cholinergic hypothesis, glutamatergic hypothesis, NMDA receptor, acetylcholinesterase, cholinergic neurons, glutamate uptake, astroglial cells, cholinesterase inhibitors, memantine, learning and memory
- MeSH terms
- Aged, Alzheimer Disease, Cholinergic Fibers, Humans, Neural Pathways, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Neurotransmitter Agents, Glutamate Plasma Membrane Transport Proteins
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