Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to β-amyloid deposition in APP/PS1 double transgenic Alzheimer mice
Open accessAbstract
The role of microglia recruited from bone marrow (BM) into the CNS during the progression of Alzheimer's disease (AD) is poorly understood. To investigate whether beta-amyloid (Abeta) associated microglia are derived from blood monocytes, we transplanted BM cells from enhanced green fluorescent protein expressing mice into young or old transgenic AD mice and determined the engraftment of BM-derived cells into the brain and their relative distribution near Abeta deposits. When young transgenic mice were transplanted before the onset of AD-like pathology and the brains analyzed 6.5 months later, the number of engrafted cells was significantly higher than in age-matched wild type mice. Moreover, the number of BM-derived cells associated with Abeta was significantly higher than in old transgenic mice transplanted after the establishment of AD-like pathology. Local inflammation caused by intrahippocampal lipopolysaccharide injection significantly increased the engraftment of BM-derived cells in old AD mice and decreased the hippocampal Abeta burden. These results suggest that infiltration of BM-derived monocytic cells into the brain contributes to the development of microglial reaction in AD.
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Peripheral macrophages are capable of traversing the blood-brain barrier during times of injury and disease.
“Furthermore, peripheral macrophages may not just be bystanders in the progression of AD, as it has been shown that they are not only more efficient phagocytes of Aβ than microglia, but they are also capable of traversing the blood-brain barrier during times of injury and disease [17–21].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [20]
Peripheral macrophages are more efficient phagocytes of Aβ than microglia.
“Furthermore, peripheral macrophages may not just be bystanders in the progression of AD, as it has been shown that they are not only more efficient phagocytes of Aβ than microglia, but they are also capable of traversing the blood-brain barrier during times of injury and disease [17–21].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [20]
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- Authors
- Malm, T. M., Koistinaho, M., Pärepalo, M., Vatanen, T., Ooka, A., Karlsson, S., & Koistinaho, J.
- Affiliations
- University of Eastern Finland (FI)
- Kuopio University Hospital (FI)
- Skåne University Hospital (SE)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 18
- Issue
- 1
- Pages
- 134-142
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W1998843397
- Cited by
- 301
- References
- 10
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 4 · 2021: 14 · 2020: 11 · 2019: 10 · 2018: 6 · 2017: 10 · 2016: 9 · 2015: 22 · 2014: 18 · 2013: 22 · 2012: 23
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- bone marrow-derived cells, microglia, amyloid-beta deposition, Alzheimer's disease, APP/PS1 mice, monocyte recruitment, cell engraftment, lipopolysaccharide-induced inflammation, hippocampus, neuroinflammation, blood-brain barrier
- MeSH terms
- Aging, Alzheimer Disease, Animals, Bone Marrow Cells, Cell Differentiation, Cell Movement, Disease Models, Animal, Encephalitis, Female, Gliosis, Hippocampus, Humans, Lipopolysaccharides, Male, Membrane Proteins, Mice, Transgenic, Recombinant Fusion Proteins, Bone Marrow Transplantation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Presenilin-1
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