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The role of inflammatory processes in Alzheimer’s disease

  • Inflammation in acute and chronic neurological and psychiatric diseases
  • Published:
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Abstract

It has become increasingly clear that inflammatory processes play a significant role in the pathophysiology of Alzheimer’s disease (AD). Neuroinflammation is characterized by the activation of astrocytes and microglia and the release of proinflammatory cytokines and chemokines. Vascular inflammation, mediated largely by the products of endothelial activation, is accompanied by the production and the release of a host of inflammatory factors which contribute to vascular, immune, and neuronal dysfunction. The complex interaction of these processes is still only imperfectly understood, yet as the mechanisms continue to be elucidated, targets for intervention are revealed. Although many of the studies to date on therapeutic or preventative strategies for AD have been narrowly focused on single target therapies, there is accumulating evidence to suggest that the most successful treatment strategy will likely incorporate a sequential, multifactorial approach, addressing direct neuronal support, general cardiovascular health, and interruption of deleterious inflammatory pathways.

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Abbreviations

ACh:

Acetylcholine

AChE:

Acetylcholinesterase

AChEI:

Acetylcholinesterase inhibitors

AGE:

Advanced glycation end product

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

AICD:

Amyloid precursor protein intracellular domain

BACE-1:

β-Site APP cleaving enzyme 1

Aβ:

β-Amyloid

BBB:

Blood–brain barrier

CNS:

Central nervous system

CD14:

Cluster of differentiation 14

COX:

Cyclooxygenase

eNOS:

Endothelial nitric oxide synthase

ET-1:

Endothelin-1

GLUT-1:

Glucose tansporter-1

GLT-1:

Glutamate transporter-1

GSK:

Glycogen synthase kinase

HPC:

Hippocampal progenitor cell

Hcy:

Homocysteine

4-HNE:

4-Hydroxynonenal

HIF-1α:

Hypoxia-inducible factor-1α

iNOS:

Inducible nitric oxide synthase

IFNγ:

Interferon-γ

IP-10:

Interferon-γ induced protein-10

IL:

Interleukin

JNK:

c-Jun N-terminal kinase

KO:

Knockout

LRP-1:

LDL-receptor related protein-1

LTP:

Long-term potentiation

LDL:

Low density lipoprotein

MCSF:

Macrophage colony stimulating factor

MMP:

Matrix metalloproteinase

MAP:

Microtubule-associated protein

MCI:

Mild cognitive impairment

MLK-3:

Mitogen-activated protein kinase kinase kinase 11

MCP-1:

Monocyte chemotactic protein-1

NFT:

Neurofibrillary tangle

NMDA:

N-methyl-d-aspartic acid

NALP3:

NACHT/LRR/PYD domains-containing protein 3

NGF:

Nerve growth factor

nNOS:

Neuronal nitric oxide synthase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NSAID:

Non-steroidal anti-inflammatory drug

NF-κB:

Nuclear factor-κB

P-gp:

P-glycoprotein

PPARγ:

Peroxisome proliferator activated receptor-γ

PS-1:

Presenilin-1

PGE2:

Prostaglandin E2

PKC:

Protein kinase C

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RAGE:

Receptor for advanced glycation end product

STAT:

Signal transducer and activator of transcription

TSP:

Thrombospondin

TIMP-1:

Tissue inhibitor of MMP

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor-α

VCAM-1:

Vascular cell-adhesion molecule

VEGF:

Vascular endothelial growth factor

WT:

Wild type

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  1. College of Osteopathic Medicine, Touro University California, 1310 Club Drive, Vallejo, CA, 94592, USA

    G. Joseph Broussard, Jennifer Mytar, Rung-chi Li & Gloria J. Klapstein

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  1. G. Joseph Broussard
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  2. Jennifer Mytar
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  3. Rung-chi Li
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  4. Gloria J. Klapstein
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Correspondence to Gloria J. Klapstein.

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Broussard, G.J., Mytar, J., Li, Rc. et al. The role of inflammatory processes in Alzheimer’s disease. Inflammopharmacol 20, 109–126 (2012). https://doi.org/10.1007/s10787-012-0130-z

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  • DOI: https://doi.org/10.1007/s10787-012-0130-z

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