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Journal of Neural Transmission

, Volume 117, Issue 8, pp 919–947 | Cite as

Neuroinflammatory processes in Alzheimer’s disease

  • Michael T. HenekaEmail author
  • M. Kerry O’Banion
  • Dick Terwel
  • Markus Peter Kummer
Basic Neurosciences, Genetics and Immunology - Review article

Abstract

Generation of neurotoxic amyloid β peptides and their deposition along with neurofibrillary tangle formation represent key pathological hallmarks in Alzheimer’s disease (AD). Recent evidence suggests that inflammation may be a third important component which, once initiated in response to neurodegeneration or dysfunction, may actively contribute to disease progression and chronicity. Various neuroinflammatory mediators including complement activators and inhibitors, chemokines, cytokines, radical oxygen species and inflammatory enzyme systems are expressed and released by microglia, astrocytes and neurons in the AD brain. Degeneration of aminergic brain stem nuclei including the locus ceruleus and the nucleus basalis of Meynert may facilitate the occurrence of inflammation in their projection areas given the antiinflammatory and neuroprotective action of their key transmitters norepinephrine and acetylcholine. While inflammation has been thought to arise secondary to degeneration, recent experiments demonstrated that inflammatory mediators may stimulate amyloid precursor protein processing by various means and therefore can establish a vicious cycle. Despite the fact that some aspects of inflammation may even be protective for bystander neurons, antiinflammatory treatment strategies should therefore be considered. Non-steroidal anti-inflammatory drugs have been shown to reduce the risk and delay the onset to develop AD. While, the precise molecular mechanism underlying this effect is still unknown, a number of possible mechanisms including cyclooxygenase 2 or γ-secretase inhibition and activation of the peroxisome proliferator activated receptor γ may alone or, more likely, in concert account for the epidemiologically observed protection.

Keywords

Alzheimer’s disease Neuroinflammation Amyloid beta Peroxisome proliferator activated receptor gamma Cytokines Locus ceruleus 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Michael T. Heneka
    • 1
    Email author
  • M. Kerry O’Banion
    • 2
  • Dick Terwel
    • 1
  • Markus Peter Kummer
    • 1
  1. 1.Department of Neurology, Clinical NeurosciencesUniversity of BonnBonnGermany
  2. 2.Department of Neurobiology and AnatomyUniversity of RochesterRochesterUSA

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