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Current Hypotheses and Research Milestones in Alzheimer's Disease pp 139–156Cite as

Participation of Glial Cells in the Pathogenesis of AD: A Different View on Neuroinflammation

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Abstract

Inflammation has been linked to Alzheimer's disease (AD). The accepted view is that inflammation is secondary to amyloid-β (Aβ) accumulation or neurodegeneration. However, I propose that glial dysfunction and the resulting imbalance between the cytotoxic inflammatory and neuroprotective-modulator activity could be the pathological mechanism behind AD. Such unbalance could be promoted by conditions like hypoxia and inflammation, which are frequently observed in aged individuals. A strong inflammatory response can promote defective processing of the amyloid-β protein precursor (AβPP) and the handling of Aβ by glial cells, resulting in the accumulation of Aβ and further inflammation. Proinflammatory conditions also enhance microglial cell activation by AβPP and Aβ and reduce astrocytes-mediated inhibition of microglial activation. These observations indicate that glial cell response to Aβ can be critically dependent on the priming of glial cells by proinflammatory factors. Astrocytes play a major role in the pathophysiology of AD, both promoting damage and mediating neuroprotection. Persistent inflammation can impair modulation and promote microglia-mediated neurotoxicity. Altogether, I propose that dysfunctional glia could result in both neuroinflammation and impaired neuronal function in AD.

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Abbreviations

Aβ:

amyloid-β

AβPP:

amyloid-β protein precursor

AD:

Alzheimer's disease

BACE 1:

β-secretase cleaving enzyme 1

CNS:

central nervous system

COX:

cyclooxygenase

COX-2:

inducible form of cyclooxygenase

ERK:

extracellular signal-regulated kinases

IFN-γ:

interferon-γ

IL-1β:

interleukin-1β

IL-6:

interleukin-6

iNOS:

inducible nitric oxide synthase

JNK:

jun N-terminal kinase

LPS:

lipopolysaccharide

LTP:

long-term potentiation

MAPKs:

mitogen-activated protein kinases

MCP-1:

monocyte chemotactic protein-1

MHC-class II:

major histocompatibility complex class II

MKP-1:

MAPK phosphatase type 1

NF-κB:

nuclear factor-κ B;

NGF:

nerve growth factor

NO:

nitric oxide

NSAIDs:

nonsteroidal anti-inflammatory drugs

ROS:

reactive oxygen species

SRs:

scavenger receptors

STAT1:

signal-transducer and activator of transcription-1

TGF-β:

transforming growth factor-β

TNF-α:

tumor necrosis factor-α

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Acknowledgments

I thank Dr. Jaime Eugenín for his longstanding support and his critical reading of the manuscript. I gratefully acknowledge technical support of G. Ramírez and support by grant 1040831 from FONDECYT to RvB.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Marcoleta 391, Chile

    Rommy von Bernhardi

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  1. Rommy von Bernhardi
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Correspondence to Rommy von Bernhardi .

Editor information

Editors and Affiliations

  1. Mind/Brain Program of the International Center of Biomedicine, University of Chile, Santiago, Chile

    Ricardo B. Maccioni

  2. School of Medicine Miami, University of Miami, Florida, USA

    Ricardo B. Maccioni

  3. College of Sciences, University of Texas at San Antonio, San Antonio, Texas, 78249-0661, USA

    George Perry

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Bernhardi, R. (2009). Participation of Glial Cells in the Pathogenesis of AD: A Different View on Neuroinflammation. In: Maccioni, R.B., Perry, G. (eds) Current Hypotheses and Research Milestones in Alzheimer's Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-87995-6_12

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