Acta Neuropathologica

, Volume 126, Issue 4, pp 461–477 | Cite as

Microglia actions in Alzheimer’s disease

  • Stefan Prokop
  • Kelly R. Miller
  • Frank L. Heppner
Review

Abstract

The identification of microglia-associated, neurological disease-causing mutations in patients, combined with studies in mouse models has highlighted microglia, the brain’s intrinsic myeloid cells, as key modulators of pathogenesis and disease progression in neurodegenerative diseases. In Alzheimer’s disease (AD) in particular, the activation and accumulation of microglial cells around β-Amyloid (Aβ) plaques has long been described and is believed to result in chronic neuroinflammation—a term that, despite being commonly used, lacks a precise definition. This seemingly directed response of microglia to amyloid deposits conflicts with the fact that the increasing buildup of Aβ plaques is not inhibited by these cells during disease progression. While recent evidence suggests that microglia lose their intrinsic beneficial function during the course of AD and may even acquire a “toxic” phenotype over time, Aβ may also simply not be an appropriate trigger to induce phagocytosis and degradation by microglia in vivo. As recent experimental evidence has indicated the importance of the microglia in AD pathogenesis, future efforts aimed at tackling this disease via utilization or modulation of microglia or factors therefrom appear to be an exciting and challenging research front.

Keywords

Microglia Alzheimer’s disease Phagocytosis Activation Cellular senescence 

Abbreviations

Amyloid-β

sAβ

Soluble Amyloid-β

AD

Alzheimer’s disease

BM–MNC

Bone marrow mononuclear cells

CCR2

C-C chemokine receptor type 2

CD

Cluster of differentiation

CNS

Central nervous system

CSFR1

Colony stimulating factor 1 receptor

CX3CR1

CX3C chemokine receptor 1

CX3CL1

Chemokine (C-X3-C motif) ligand 1 (Fraktalkine)

GWAS

Genome wide association study

HDLS

Hereditary diffuse leukoencephalopathy with spheroids

HLA

Human leucocyte antigen

HSVTK

Herpes-simplex virus thymidine kinase

IL

Interleukin

LOAD

Late-onset Alzheimer’s disease

LPS

Lipopolysaccharide

MCP1

Monocyte chemoattractant protein 1

M-CSF

Macrophage colony-stimulating factor

MHC

Major histocompatibility complex

MIP

Macrophage inflammatory protein

MPL

Monophosphoryl lipid A

NALP3

NACHT, LRR and PYD domains-containing protein 3

NSAIDS

Nonsteroidal anti-inflammatory drugs

RAGE

Receptor for advanced glycation end products

TREM2

Triggering receptor expressed on myeloid cells 2

TNF

Tumor necrosis factor

TGF

Transforming growth factor

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Stefan Prokop
    • 1
  • Kelly R. Miller
    • 1
  • Frank L. Heppner
    • 1
  1. 1.Department of NeuropathologyCharité, Universitätsmedizin BerlinBerlinGermany

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