Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer’s disease
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Significance: We demonstrate that depletion of blood plasminogen is sufficient to protect against both innate immune cell activation in the brain and Alzheimer’s disease (AD) pathology in a mouse model of AD. This work provides a molecular mechanism for initiation of AD-related brain inflammation and for regulation of β-amyloid deposition, and could lead to therapeutic strategies in human AD patients, including the targeting of systemic molecules.
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The benefits of GPLD1 and other exerkines on brain structure and function may relate to peripheral effects such as complement signalling or coagulation.
“Hence, the benefit of GPLD1 (REF.148) and other exerkines on brain structure and function might relate to its peripheral effects, such as the complement signalling cascade149,158, or coagulation159.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [159]
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- Authors
- Baker, S. K., Chen, Z.-L., Norris, E. H., Revenko, A. S., MacLeod, A. R., & Strickland, S.
- Affiliations
- Rockefeller University (US)
- Ionis Pharmaceuticals (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-09-25
- Volume
- 115
- Issue
- 41
- Pages
- E9687-E9696
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6187132
- OpenAlex
- W2893444607
- Cited by
- 68
- References
- 74
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 11 · 2022: 4 · 2021: 17 · 2020: 14 · 2019: 8 · 2018: 1
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NS106668)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, plasminogen, plasmin, neuroinflammation, amyloid plaques, antisense oligonucleotides, alpha2-antiplasmin, glial activation, systemic inflammation, mouse models of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Inflammation, Mice, Transgenic, Plasminogen, Amyloid beta-Peptides, Oligodeoxyribonucleotides, Antisense, Mice
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