Neuroinflammation in Alzheimer's Disease and Parkinson's Disease

Are Microglia Pathogenic in Either Disorder?

Joseph Rogers, Diego Mastroeni, Brian Leonard, Jeffrey Joyce, Andrew Grover

Research output: Chapter in Book/Report/Conference proceedingChapter

180 Citations (Scopus)

Abstract

Microglial activation similar to that which occurs in peripheral macrophages during inflammatory attack was first demonstrated in the Alzheimer's disease (AD) brain two decades ago. Localization to pathologically vulnerable regions of AD cortex, localization to sites of specific AD pathology such as amyloid-β peptide (Aβ) deposits, and the ability of activated microglia to release toxic inflammatory factors suggested that the activation of microglia in AD might play a pathogenic role. However, proving this hypothesis in a disease in which so many profound pathologies occur (e.g., Aβ deposition, neurofibrillary tangle formation, inflammation, neuronal loss, neuritic loss, synaptic loss, neuronal dysfunction, vascular alterations) has proven difficult. Although investigations of microglia in Parkinson's disease (PD) are more recent and therefore less extensive, demonstration of a pathogenic role for microglial activation may actually be much simpler in PD than AD because the root pathological event in PD, loss of dopamine (DA)-secreting substantia nigra neurons, is already well established. Indeed, indirect but converging evidence of a pathogenic role for activated microglia in PD has already begun to emerge. The nigra reportedly has the highest density of microglia in brain, and, in PD, nigral microglia are not only highly activated but also highly clustered around dystrophic DA neurons. 6-OHDA and MPTP models of PD in rodents induce substantia nigra microglial activation. More cogent, injections of the classic microglial/macrophage activator lipopolysaccharide into or near the rodent nigra cause a specific loss of DA neurons there. Culture models with human microglia and human cellular targets replicate this phenomenon. Notably, nearly all the proposed etiologies of PD, including brain bacterial and viral exposure, pesticides, drug contaminants, and repeated head trauma, are known to cause brain inflammation. A mechanism by which activated microglia might specifically target DA neurons remains a critical missing link in the proof of a pathogenic role for activated microglia in PD. If such a link could be established, however, clinical intervention trials with agents that dampen microglial activation might be warranted in PD.

Original languageEnglish (US)
Title of host publicationNeuroinflation in Neuronal Death and Repair
EditorsGiacinto Bagetta, Tiziana Corasaniti, Stuart Lipton
Pages235-246
Number of pages12
DOIs
StatePublished - Aug 2 2007
Externally publishedYes

Publication series

NameInternational Review of Neurobiology
Volume82
ISSN (Print)0074-7742

Fingerprint

Microglia
Parkinson Disease
Alzheimer Disease
Dopaminergic Neurons
Substantia Nigra
Rodentia
Brain
Macrophages
Pathology
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Neurofibrillary Tangles
Aptitude
Poisons
Oxidopamine
Encephalitis
Craniocerebral Trauma
Amyloid
Pesticides
Blood Vessels
Lipopolysaccharides

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

Cite this

Rogers, J., Mastroeni, D., Leonard, B., Joyce, J., & Grover, A. (2007). Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder? In G. Bagetta, T. Corasaniti, & S. Lipton (Eds.), Neuroinflation in Neuronal Death and Repair (pp. 235-246). (International Review of Neurobiology; Vol. 82). https://doi.org/10.1016/S0074-7742(07)82012-5

Neuroinflammation in Alzheimer's Disease and Parkinson's Disease : Are Microglia Pathogenic in Either Disorder? / Rogers, Joseph; Mastroeni, Diego; Leonard, Brian; Joyce, Jeffrey; Grover, Andrew.

Neuroinflation in Neuronal Death and Repair. ed. / Giacinto Bagetta; Tiziana Corasaniti; Stuart Lipton. 2007. p. 235-246 (International Review of Neurobiology; Vol. 82).

Research output: Chapter in Book/Report/Conference proceedingChapter

Rogers, J, Mastroeni, D, Leonard, B, Joyce, J & Grover, A 2007, Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder? in G Bagetta, T Corasaniti & S Lipton (eds), Neuroinflation in Neuronal Death and Repair. International Review of Neurobiology, vol. 82, pp. 235-246. https://doi.org/10.1016/S0074-7742(07)82012-5
Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A. Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder? In Bagetta G, Corasaniti T, Lipton S, editors, Neuroinflation in Neuronal Death and Repair. 2007. p. 235-246. (International Review of Neurobiology). https://doi.org/10.1016/S0074-7742(07)82012-5
Rogers, Joseph ; Mastroeni, Diego ; Leonard, Brian ; Joyce, Jeffrey ; Grover, Andrew. / Neuroinflammation in Alzheimer's Disease and Parkinson's Disease : Are Microglia Pathogenic in Either Disorder?. Neuroinflation in Neuronal Death and Repair. editor / Giacinto Bagetta ; Tiziana Corasaniti ; Stuart Lipton. 2007. pp. 235-246 (International Review of Neurobiology).
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