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Cited by 69Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

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Akyuz, Enes, Arulsamy, Alina, Aslan, Feyza Sule, Sarisözen, Bugra, Guney, Beyzanur, Hekimoglu, Abdulhekim, Yilmaz, Beyza Nur, Retinasamy, Thaarvena +1 more·2025·Molecular Neurobiology
DOI 10.1007/s12035-024-04333-yPMC PMC11772559
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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for the pathogenesis of the disease. The accumulation of Aβ plaques and tau affect the balance in chemical neurotransmitters in the brain. Thus, the current review examined the role of neurotransmitters in the pathogenesis of Alzheimer’s disease and discusses the alterations in the neurochemical activity and cross talk with their receptors and transporters. In the presence of Aβ plaques and neurofibrillary tangles, changes may occur in the expression of neuronal receptors which in turn triggers excessive release of glutamate into the synaptic cleft contributing to cell death and neuronal damage. The GABAergic system may also be affected by AD pathology in a similar way. In addition, decreased receptors in the cholinergic system and dysfunction in the dopamine neurotransmission of AD pathology may also contribute to the damage to cognitive function. Moreover, the presence of deficiencies in noradrenergic neurons within the locus coeruleus in AD suggests that noradrenergic stimulation could be useful in addressing its pathophysiology. The regulation of melatonin, known for its effectiveness in enhancing cognitive function and preventing Aβ accumulation, along with the involvement of the serotonergic system and histaminergic system in cognition and memory, becomes remarkable for promoting neurotransmission in AD. Additionally, nitric oxide and adenosine-based therapeutic approaches play a protective role in AD by preventing neuroinflammation. Overall, neurotransmitter-based therapeutic strategies emerge as pivotal for addressing neurotransmitter homeostasis and neurotransmission in the context of AD. This review discussed the potential for neurotransmitter-based drugs to be effective in slowing and correcting the neurodegenerative processes in AD by targeting the neurochemical imbalance in the brain. Therefore, neurotransmitter-based drugs could serve as a future therapeutic strategy to tackle AD.

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  • Increasing evidence suggests that excitotoxicity may arise early in AD, potentially preceding overt amyloid and tau pathology, raising the possibility that earlier therapeutic intervention could yield greater benefits.

    “Increasing evidence suggests that excitotoxicity may arise early in AD, potentially preceding overt amyloid and tau pathology, raising the possibility that earlier therapeutic intervention could yield greater benefits [120].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [120]

    The Glutamate section (page unavailable) links excessive glutamate and NMDA-receptor activity to neuronal damage in AD and proposes detecting glutamate abnormalities to enable time-specific interventions. It does not say excitotoxicity precedes overt amyloid and tau pathology or that earlier treatment would yield greater benefits; the glutamate changes it describes are aligned with developing amyloid plaques. (LLM, conf=0.83)

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Authors
Akyuz, E., Arulsamy, A., Aslan, F. S., Sarisözen, B., Guney, B., Hekimoglu, A., Yilmaz, B. N., Retinasamy, T., & Shaikh, M. F.
Affiliations
  • Monash University Malaysia (MY)
  • Tekirdağ Namık Kemal University (TR)
  • Marmara University (TR)
  • Sağlık Bilimleri Üniversitesi (TR)
Corresponding author
  • Arulsamy, Alina
  • Shaikh, Mohd. Farooq
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2024-07-16
Volume
62
Issue
2
Pages
1631-1674
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-024-04333-y
PMC
PMC11772559
OpenAlex
W4400683522
Cited by
69
References
26
Citations by year
2026: 42 · 2025: 24 · 2024: 3
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurobiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Monash University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, neurotransmitters, neurotransmitter imbalance, amyloid plaques, neurofibrillary tangles, glutamate excitotoxicity, GABAergic system, cholinergic system, dopamine, noradrenergic system, locus coeruleus, melatonin, serotonergic system, histaminergic system, nitric oxide, adenosine, neuroinflammation, neurotransmission
MeSH terms
Alzheimer Disease, Animals, Humans, Synaptic Transmission, Neurotransmitter Agents

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