Synaptic Plasticity, Dementia and Alzheimer Disease
Abstract
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment. Degenerative diseases of the human brain continue to pose one of biomedicine's most intractable problems. Research on human neurodegeneration is now moving from descriptive to mechanistic analyses. At the same time, it is increasing apparently that morphological lesions traditionally used by neuropathologists to confirm post-mortem clinical diagnosis might furnish us with an experimentally tractable handle to understand causative pathways. Consider the aging-dependent neurodegenerative disorder Alzheimer's disease (AD) which is characterised at the neuropathological level by deposits of insoluble amyloid β-peptide (Aβ) in extracellular plaques and aggregated tau protein, which is found largely in the intracellular neurofibrillary tangles. We now appreciate that mild cognitive impairment in early AD may be due to synaptic dysfunction caused by accumulation of non-fibrillar, oligomeric Aβ, occurring well in advance of evident widespread synaptic loss and neurodegeneration. Soluble Aβ oligomers can adversely affect synaptic structure and plasticity at extremely low concentrations, although the molecular substrates by which synaptic memory mechanisms are disrupted remain to be fully elucidated. The dendritic spine constitutes a primary locus of excitatory synaptic transmission in the mammalian central nervous system. These structures protruding from dendritic shafts undergo dynamic changes in number, size and shape in response to variations in hormonal status, developmental stage, and changes in afferent input. It is perhaps not unexpected that loss of spine density may be linked to cognitive and memory impairment in AD, although the underlying mechanism(s) remain uncertain. This article aims to present a critical overview of current knowledge on the bases of synaptic dysfunction in neurodegenerative diseases, with a focus on AD, and will cover amyloid- and nonamyloid- driven mechanisms. We will consider also emerging data dealing with potential therapeutic approaches for ameliorating the cognitive and memory deficits associated with these disorders.
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Even more targeted strategies are being developed to enhance neurotransmitter activity.
“Even more targeted strategies are being developed to enhance neurotransmitter activity.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [210]
Medications that may improve synaptic function include those that allosterically increase the M1 muscarinic acetylcholine receptor.
“Examples of medications that may improve synaptic function include those that allosterically increase the M1 muscarinic acetylcholine receptor [209,210].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [210]
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“It has been shown that soluble Aβ oligomers may adversely affect synaptic structure and plasticity at very low concentrations [73].”
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“closely related, synapse loss and Tau pathology are hallmarks of AD and other tauopathies (Yoshiyama et al., 2007; Skaper et al., 2017; Dejanovic et al., 2018; Kurucu et al., 2022).”
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The Potential Role of miRNAs in Cognitive Frailty
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“discovered that Aβ led to impaired hippocampal long-term potentiation and compromised synaptic plasticity [11], which was considered as a major correlate of dementia [12].”
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- Authors
- Skaper, S. D., Facci, L., Zusso, M., & Giusti, P.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Giusti, Pietro
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2017-04-12
- Volume
- 16
- Issue
- 3
- Pages
- 220-233
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2573085547
- Cited by
- 192
- References
- 0
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 27 · 2023: 30 · 2022: 33 · 2021: 25 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 3
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- synaptic plasticity, Alzheimer's disease, dementia, neurodegeneration, amyloid-beta oligomers, tau protein, dendritic spines, synaptic dysfunction, long-term potentiation, synaptogenesis, axonal sprouting, neurogenesis, mild cognitive impairment, memory impairment, treatment options
- MeSH terms
- Alzheimer Disease, Dementia, Humans, Neuronal Plasticity, Synapses
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