Cited by 59Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsPhagocytosis and Immune Regulation

Scavenger Receptor-A deficiency impairs immune response of microglia and astrocytes potentiating Alzheimer’s disease pathophysiology

Cornejo, Francisca, Vruwink, Marianne, Metz, Claudia, Muñoz, Paola, Salgado, Nicole, Poblete, Joaquín, Andrés, María Estela, Eugenín, Jaime +1 more·2018·Brain, Behavior, and Immunity

Abstract

Late onset Alzheimer disease's (LOAD) main risk factor is aging. Although it is not well known which age-related factors are involved in its development, evidence points out to the involvement of an impaired amyloid-β (Aβ) clearance in the aged brain among possible causes. Glial cells are the main scavengers of the brain, where Scavenger Receptor class A (SR-A) emerges as a relevant player in AD because of its participation in Aβ uptake and in the modulation of glial cell inflammatory response. Here, we show that SR-A expression is reduced in the hippocampus of aged animals and APP/PS1 mice. Given that Aβ deposition increases in the aging brain, we generated a triple transgenic mouse, which accumulates Aβ and is knockout for SR-A (APP/PS1/SR-A-/-) to evaluate Aβ accumulation and the inflammatory outcome of SR-A depletion in the aged brain. The lifespan of APP/PS1/SR-A-/- mice was greatly reduced, accompanied by a 3-fold increase in plasmatic pro-inflammatory cytokines, and reduced performance in a working memory behavioral assessment. Microglia and astrocytes lacking SR-A displayed impaired oxidative response and nitric oxide production, produced up to 7-fold more pro-inflammatory cytokines and showed a 12-fold reduction in anti-inflammatory cytokines release, with conspicuous changes in lipopolysaccharide-induced glial activation. Isolated microglia from young and adult mice lacking SR-A showed a 50% reduction in phagocytic activity. Our results indicate that reduced expression of SR-A can deregulate glial inflammatory response and potentiate Aβ accumulation, two mechanisms that could contribute to AD progression.

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Crossref · 10.1016/j.bbi.2017.12.007

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  • Loss of SR-A1 lowers microglial Aβ uptake by 60% and raises mortality and Aβ accumulation.

    “SR-A1-deficiency decreases microglial Aβ uptake by 60%37,136 and increases mortality and Aβ accumulation37,136”

    From Microglia in neurodegeneration (2018) · cites this paper as [136]

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Authors
Cornejo, F., Vruwink, M., Metz, C., Muñoz, P., Salgado, N., Poblete, J., Andrés, M. E., Eugenín, J., & von Bernhardi, R.
Affiliations
  • Pontificia Universidad Católica de Chile (CL)
  • Universidad de Santiago de Chile (CL)
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2018-03
Volume
69
Pages
336-350
ISSN
0889-1591 (ISSN-L)
OpenAlex
W2772306958
Cited by
59
References
96
Citations by year
2026: 4 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 3
FWCI
2.05
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Comisión Nacional de Investigación Científica y Tecnológica
  • Fondo Nacional de Desarrollo Científico y Tecnológico
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
scavenger receptor A, Alzheimer's disease, amyloid-beta clearance, microglia, astrocytes, glial inflammation, aging, inflammatory cytokines, nitric oxide, oxidative response, phagocytosis, working memory, hippocampus
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Brain, Disease Models, Animal, Memory, Short-Term, Mice, Transgenic, Nitric Oxide, Cytokines, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Oxidative Stress, Scavenger Receptors, Class A, Mice

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