Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease

Dinkins, Michael B.; Dasgupta, Somsankar; Wang, Guanghu; Zhu, Gu; Bieberich, Erhard

doi:10.1016/j.neurobiolaging.2014.02.012

Cited by 494Alzheimer's disease research and treatmentsExtracellular vesicles in diseaseNeuroinflammation and Neurodegeneration Mechanisms

Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease

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Dinkins, Michael B., Dasgupta, Somsankar, Wang, Guanghu, Zhu, Gu, Bieberich, Erhard·2014·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2014.02.012PMC PMC4035236

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Abstract

We present evidence here that exosomes stimulate aggregation of amyloid beta (Aβ)1-42 in vitro and in vivo and interfere with uptake of Aβ by primary cultured astrocytes and microglia in vitro. Exosome secretion is prevented by the inhibition of neutral sphingomyelinase 2 (nSMase2), a key regulatory enzyme generating ceramide from sphingomyelin, with GW4869. Using the 5XFAD mouse, we show that intraperitoneal injection of GW4869 reduces the levels of brain and serum exosomes, brain ceramide, and Aβ1-42 plaque load. Reduction of total Aβ1-42 as well as number of plaques in brain sections was significantly greater (40% reduction) in male than female mice. Our results suggest that GW4869 reduces amyloid plaque formation in vivo by preventing exosome secretion and identifies nSMase2 as a potential drug target in AD by interfering with exosome secretion.

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Astrocyte-derived exosomes drive neurodegeneration of AD through the acceleration of Aβ aggregation in vivo.
“In addition, it has been found that astrocyte-derived exosomes drive neurodegeneration of AD through the acceleration of Aβ aggregation in vivo [205].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [205]

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Authors: Dinkins, M. B., Dasgupta, S., Wang, G., Zhu, G., & Bieberich, E.
Affiliations: Augusta University (US)
Corresponding author: Bieberich, Erhard
ORCID: Dasgupta, Somsankar
Wang, Guanghu
Bieberich, Erhard
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2014-08
Volume: 35
Issue: 8
Pages: 1792-1800
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2014.02.012
PMC: PMC4035236
OpenAlex: W1991931811
Cited by: 494
References: 58
Citations by year: 2026: 24 · 2025: 32 · 2024: 49 · 2023: 44 · 2022: 63 · 2021: 74 · 2020: 58 · 2019: 43 · 2018: 28 · 2017: 29 · 2016: 28 · 2015: 17 · 2014: 4
FWCI: 17.29
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (R01-AG034389)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: exosomes, amyloid-beta 42, amyloid plaques, Alzheimer's disease, 5xFAD mice, neutral sphingomyelinase 2, GW4869, ceramide, exosome secretion, astrocytes, microglia, sex differences
MeSH terms: Alzheimer Disease, Aniline Compounds, Animals, Astrocytes, Benzylidene Compounds, Brain, Cells, Cultured, Ceramides, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Peptide Fragments, Sphingomyelin Phosphodiesterase, Amyloid beta-Peptides, Microglia, Exosomes, Plaque, Amyloid, Molecular Targeted Therapy, Protein Aggregation, Pathological

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Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease

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