ArticleBMC medicine2024
Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer's disease.
Article in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Markers and Enrichment Strategies for Brain-Derived Extracellular Vesicles: Current Evidence, Limitations and Future Directions.Neuromolecular medicine · 2026Review
- Extracellular vesicles derived from astrocytes pretreated with melatonin promoted neuro-angiogenesis in mice with ischemic medial prefrontal cortex.Journal of translational medicine · 2026Article
- Microglia-Neuron Interactions in Alzheimer's Disease.Current neuropharmacology · 2026Review
- Toward nanomedicine-enabled RNA therapeutics for Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Oxidative stress-driven disease-associated microglia (DAM)-like polarization in human microglia (HMC3) cells exposed to small-size silver nanoparticles in a transwell co-culture system with neurons (cholinergic differentiated SH-SY5Y) cells in vitro.Archives of toxicology · 2026Article
- Plasma growth-associated protein 43 correlates with synaptic loss in Alzheimer's disease.Cell reports. Medicine · 2025Article
- Extracellular vesicle-based therapies for neurodegenerative diseases.NeuroImmune pharmacology and therapeutics · 2025Review
- Review
- Surface Problem: Unveiling Extracellular Vesicles Surface Markers and Their Implications for Central Nervous System Diseases' Diagnosis and Treatment.Molecular neurobiology · 2025Review
- Extracellular Vesicles-Dependent Secretion Regulates Intracellular CYFIP2 Protein Homeostasis in Cortical Neurons.Biomedicines · 2025Article
- Extracellular Vesicles for the Treatment of Alzheimer's Disease: A Systematic Review.Journal of extracellular biology · 2025Article
- Increased Expression of Synaptic Vesicle Glycoprotein 2A (SV2A) in the Brain of Chronic Diabetic Rats.Synapse (New York, N.Y.) · 2025Article
- The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- An Overview on the Physiopathology of the Blood-Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery.Pharmaceutics · 2024Review
- Article
- Extracellular Vesicles: A Promising Therapeutic Approach to Alzheimer's Disease.Current Alzheimer research · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSynaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD.
methodsIn this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated.
resultsThe results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects.
conclusionsSynaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.
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