Novel approaches to increase synaptic resilience as potential treatments for Alzheimer’s disease
Open accessAbstract
A significant proportion of brains with Alzheimer's disease pathology are obtained from patients that were cognitively normal, suggesting that differences within the brains of these individuals made them resilient to the disease. Here, we describe recent approaches that specifically increase synaptic resilience, as loss of synapses is considered to be the first change in the brains of Alzheimer's patients. We start by discussing studies showing benefit from increased expression of neurotrophic factors and protective genes. Methods that effectively make dendritic spines stronger, specifically by acting through actin network proteins, scaffolding proteins and inhibition of phosphatases are described next. Importantly, the therapeutic strategies presented in this review tackle Alzheimer's disease not by targeting plaques and tangles, but instead by making synapses resilient to the pathology associated with Alzheimer's disease, which has tremendous potential.
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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 [209]
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 [209]
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Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
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“Examples of medications that may improve synaptic function include those that allosterically increase the M1 muscarinic acetylcholine receptor [209,210].”
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“While the study of these genes has been focused on their role in regulating spine morphology to preserve synapses [51, 74, 99], the literature also highlights their crucial involvement in microglial motility [18, 20].”
Background
- Authors
- Pham, A. Q., & Dore, K.
- Affiliations
- University of California San Diego (US)
- ORCID
- Pham, Andrew Q.
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 139
- Pages
- 84-92
- ISSN
- 1084-9521 (ISSN-L)
- PMC
- PMC10191447
- OpenAlex
- W4221026792
- Cited by
- 21
- References
- 140
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 269 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Seminars in Cell and Developmental Biology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute on Aging
- University of California San Diego (RF1 AG067049)
- National Institutes of Health
- 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
- Alzheimer's disease, synaptic loss, neurotrophic factors, protective genes, dendritic spines, actin cytoskeleton, scaffold proteins, phosphatase inhibition
- MeSH terms
- Actins, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Mice, Transgenic, Synapses, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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