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Toll-Like Receptors in Alzheimer's Disease

  • Gary E. Landreth
  • Erin G. Reed-Geaghan
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 336)

Abstract

Alzheimer’s disease (AD) is characterized by the formation of insoluble deposits of β-amyloid (Aβ) within the parenchyma of the brain. These deposits are associated with a robust microglia-mediated inflammatory response. Recent work has demonstrated that Toll-like receptors (TLRs) participate in this inflammatory response. This chapter reviews the mechanisms whereby TLRs contribute to the induction of a microglial inflammatory response to promote AD pathogenesis. Specifically, the involvement of CD14 and the TLRs in microglial activation is delineated. The TLR-mediated microglial response has beneficial roles in stimulating phagocytosis as well as detrimental roles in the Aβ-stimulated release of neurotoxic products.

Keywords

Microglial Activation Amyloid Precursor Protein Innate Immune Receptor Murine Microglia Proinflammatory Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

β-Amyloid

AD

Alzheimer’s disease

APP

Amyloid precursor protein

BACE

β-Secretase

FPRL1

Formyl peptide receptor-like 1

IFN

Interferon

IL

Interleukin

IRAK

IL-1 receptor-associated kinase

IRF

Interferon regulatory factor

MAPK

Mitogen-activated protein kinase

MHC II

Major histocompatibility complex II

mFPR2

Murine formyl peptide receptor 2

MyD88

Myeloid differentiation primary response gene 88

NSAIDs

Nonsteroidal anti-inflammatory drugs

PRRs

Pattern recognition receptors

PAMPs

Pathogen-associated molecular patterns

RIP1

Receptor-interacting protein 1

TABs

TAK1-binding proteins

TAK

TGF-β-activated kinase

TBK1

TRAF family member-associated NF-κB activator binding kinase 1

TGF-β

Transforming growth factor-β

Th2

T-helper 2

TIR

Toll/IL-1 receptor

TIRAP/MAL

TIR-containing adaptor protein/MyD88 adaptor-like

TNF-α

Tumor necrosis factor α

TLRs

Toll-like receptors

TRAF

TNF-associated factor

TRAM/TICAM2

TIR-domain-containing adaptor molecule/TRIF-related adaptor molecule 2

TRIF/TICAM

1 TIR-containing adaptor inducing IFN-β/TIR-domain containing adaptor molecule 1

Notes

Acknowledgments

This work was supported by the NIA (AG16047), the Blanchette Hooker Rockefeller Foundation, and the American Health Assistance Foundation. Erin Reed-Geaghan is supported by a predoctoral Ruth L. Kirschstein National Research Service Award (F31NS057867) from the NINDS.

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Alzheimer Research Laboratory, Department of NeurosciencesCase Western Reserve UniversityClevelandUSA

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