Cited by 132Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging

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Condello, Carlo, Yuan, Peng, Grutzendler, Jaime·2018·Biological Psychiatry

DOI 10.1016/j.biopsych.2017.10.007PMC PMC5767550

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Abstract

Recent genetic studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathophysiology of Alzheimer's disease (AD). However, the precise mechanisms by which microglia alter the course of AD neuropathology remain poorly understood. Here we discuss current evidence of the neuroprotective functions of microglia with a focus on optical imaging studies that have revealed a role of these cells in the encapsulation of amyloid deposits ("microglia barrier"). This barrier modulates the degree of plaque compaction, amyloid fibril surface area, and insulation from adjacent axons thereby reducing neurotoxicity. We discuss findings implicating genetic variants of the microglia receptor, triggering receptor expressed on myeloid cells 2, in the increased risk of late onset AD. We provide evidence that increased AD risk may be at least partly mediated by deficient microglia polarization toward amyloid deposits, resulting in ineffective plaque encapsulation and reduced plaque compaction, which is associated with worsened axonal pathology. Finally, we propose possible avenues for therapeutic targeting of plaque-associated microglia with the goal of enhancing the microglia barrier and potentially reducing disease progression.

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Crowded Cell-like Environment Accelerates the Nucleation Step of Amyloidogenic Protein Misfolding
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More evidence for association of a rare TREM2 mutation (R47H) with Alzheimer's disease risk
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Authors: Condello, C., Yuan, P., & Grutzendler, J.
Affiliations: University of California, San Francisco (US)
Stanford University (US)
Yale University (US)
Corresponding author: Grutzendler, Jaime
ORCID: Condello, Carlo
Yuan, Peng
Grutzendler, Jaime
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2018-02
Volume: 83
Issue: 4
Pages: 377-387
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2017.10.007
PMC: PMC5767550
OpenAlex: W2764165275
Cited by: 131
References: 155
Citations by year: 2026: 12 · 2025: 18 · 2024: 17 · 2023: 10 · 2022: 17 · 2021: 19 · 2020: 10 · 2019: 17 · 2018: 11
FWCI: 1.00
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Biological Psychiatry (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders: National Institutes of Health (5r01hl106815-06)
National Institute on Aging (R21AG048181, R01AG027855, RF1AG058257, P50AG047270)
National Heart, Lung, and Blood Institute (R01-HL106815)
National Institute of Neurological Disorders and Stroke (R01NS089734)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: microglia, neuroprotection, TREM2, Alzheimer's disease, amyloid plaques, amyloid fibrils, axonal pathology, microglial polarization, microglia-targeted therapy, optical imaging
MeSH terms: Neuroprotection, Alzheimer Disease, Animals, Humans, Membrane Glycoproteins, Receptors, Immunologic, Microglia, Optical Imaging

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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging

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