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

The DOI matches its Crossref record; 155 of the 155 references it cites were found in a registry or an index.

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

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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Metadata

Authors
Condello, C., Yuan, P., & Grutzendler, J.
Affiliations
  • University of California, San Francisco (US)
  • Stanford University (US)
  • Yale University (US)
Corresponding author
Grutzendler, Jaime
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2018-02
Volume
83
Issue
4
Pages
377-387
ISSN
0006-3223 (ISSN-L)
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
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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