Chronic inflammatory reactions are present in most age-related neurodegenerative disorders, including Alzheimer's disease. Over many years, a protein called amyloid-beta (Aβ) forms sticky "plaques" in the brains of people with Alzheimer's disease, ultimately killing the surrounding neurons and causing memory loss and other cognitive problems.
Inflammation or excessive action of the brain's immune cells — glial cells — is another hallmark of Alzheimer's disease. Researchers have generally assumed that inflammation equates with injury and toxicity to neurons, but the relationship among glial cells, neurons and amyloid plaques remains unclear.
Inflammatory mediators released by glial cells can be directly toxic to neurons, so they have been implicated as mediators of neurodegeneration. In Alzheimer's disease, it has been hypothesized that these inflammatory cytokines can potentially promote further Aβ plaque accumulation.
The laboratory of Pritam Das, Ph.D., at Mayo Clinic in Florida has generated a wealth of data showing that overexpression of inflammatory cytokines (such as IL-6, IFNγ and TNFα) does not increase Aβ plaque generation. Instead, these inflammatory cytokines significantly "prevent" amyloid deposition in mice. As opposed to the proinflammatory cytokines, recent data using adeno-associated virus-mediated expression of anti-inflammatory cytokines shows significantly increased Aβ plaque loads.
Based on these data and data generated by others, Dr. Das' laboratory hypothesizes that depending on the timing and context, the actions of individual cytokines or chemokines may produce divergent and unexpected effects during the disease process, but it may be possible to harness these immunomodulatory effects to beneficially alter the Alzheimer's disease phenotype.
Studies in Dr. Das' laboratory will provide valuable insight into how neuroinflammatory and immunomodulatory reactions affect amyloid deposition and tau protein dysfunction, the two hallmark pathological features of Alzheimer's disease.
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