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Toll-like Receptors: Roles in Infection and Neuropathology pp 137–153Cite as

Toll-Like Receptors in Alzheimer's Disease

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Part of the book series: Current Topics in Microbiology and Immunology ((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.

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Abbreviations

Aβ:

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

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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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  1. Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University, Cleveland, OH, 44106, USA

    Gary E. Landreth & Erin G. Reed-Geaghan

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Correspondence to Gary E. Landreth .

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  1. Dept. Pathology & Microbiology, University of Nebraska Medical Center, S. 42nd St. 600 , Omaha, 68198-3135, U.S.A.

    Tammy Kielian

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Landreth, G.E., Reed-Geaghan, E.G. (2009). Toll-Like Receptors in Alzheimer's Disease. In: Kielian, T. (eds) Toll-like Receptors: Roles in Infection and Neuropathology. Current Topics in Microbiology and Immunology, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00549-7_8

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