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Why Reducing Brain Tissue Inflammation Is Good for Our Minds

Neuroinflammation may unleash tau in ways that lead to cognitive impairment.

Key points

  • Brain tissue inflammation (i.e., neuroinflammation) is strongly associated with neurodegenerative diseases and cognitive impairment.
  • New research suggests that neuroinflammation interacts with amyloid plaques in a way that unleashes tau and drives Alzheimer's progression.
  • Another recent study found that the "exercise hormone" irisin can reduce neuroinflammation and may offset cognitive decline.
Source: ArchOnez/Shutterstock

Activated microglia releases inflammatory cytokines that trigger brain tissue inflammation. Emerging evidence suggests that the neuroinflammation associated with microglial activation might play a role in the spread of tau tangles commonly seen in the brains of patients with Alzheimer's disease (AD).

New research from the University of Pittsburgh tested the hypothesis that the combination of microglial activation (which triggers neuroinflammation) and amyloid plaque (Aβ) accumulation may unleash tau in a way that impairs cognition. These findings (Pascoal et al., 2021) were published on August 26 in the peer-reviewed journal Nature Medicine.

"We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for microglial activation, Aβ, and tau pathologies," the authors explain in their paper's abstract.

Neuroinflammation + Aβ + Unleashed Tau = Cognitive Impairment

Pascoal et al. found that the co-occurrence of neuroinflammation, amyloid plaque build-up, and tau propagation was the strongest predictor of cognitive impairment in their study population. "Our findings support a model where an interaction between Aβ and activated microglia sets the pace for tau spread," the authors note.

"Many elderly people have amyloid plaques in their brains but never progress to developing Alzheimer's disease," first author Tharick Pascoal, assistant professor of psychiatry and neurology at Pitt, said in a news release. "We know that amyloid accumulation on its own is not enough to cause dementia—our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment."

"Our research suggests that combination therapy aimed to reduce amyloid plaque formation and limit neuroinflammation might be more effective than addressing each pathology individually," he concludes.

The "Exercise Hormone" Irisin Reduces Neuroinflammation

Another recent study by researchers at Harvard Medical School found that the so-called "exercise hormone" (a.k.a. irisin or FNDC5) produced by skeletal muscles during exercise and reduces brain tissue inflammation shows promise as a therapeutic agent to offset cognitive decline. These findings (Islam et al., 2021) were published on August 20 in the peer-reviewed journal Nature Metabolism.

In this multi-pronged mouse study, researchers at Harvard's Massachusetts General Hospital used an Alzheimer's model in mice to investigate if delivering a bottled version of irisin directly into the bloodstream had brain-boosting benefits. Notably, the researchers found that irisin appeared to increase cognitive performance by reducing neuroinflammation.

"Since irisin does not specifically target amyloid plaques, but rather neuroinflammation directly, we're optimistic it could have beneficial effects on neurodegenerative diseases beyond just Alzheimer's," senior author Christiane Wrann said in a news release.

Taken together, the latest research suggests that targeting neuroinflammation may have therapeutic value as a previously underestimated way to offset cognitive decline and treat patients with AD.


Tharick A. Pascoal, Andrea L. Benedet, Nicholas J. Ashton, Min Su Kang, Joseph Therriault, Mira Chamoun, Melissa Savard, Firoza Z. Lussier, Cécile Tissot, Thomas K. Karikari, Julie Ottoy, Sulantha Mathotaarachchi, Jenna Stevenson, Gassan Massarweh, Michael Schöll, Mony J. de Leon, Jean-Paul Soucy, Paul Edison, Kaj Blennow, Henrik Zetterberg, Serge Gauthier & Pedro Rosa-Neto. "Microglial Activation and Tau Propagate Jointly Across Braak Stages." Nature Medicine (First published: August 26, 2021) DOI: 10.1038/s41591-021-01456-w

Mohammad R. Islam, Sophia Valaris, Michael F. Young, Erin B. Haley, Renhao Luo, Sabrina F. Bond, Sofia Mazuera, Robert R. Kitchen, Barbara J. Caldarone, Luis E. B. Bettio, Brian R. Christie, Angela B. Schmider, Roy J. Soberman, Antoine Besnard, Mark P. Jedrychowski, Hyeonwoo Kim, Hua Tu, Eunhee Kim, Se Hoon Choi, Rudolph E. Tanzi, Bruce M. Spiegelman & Christiane D. Wrann. "Exercise Hormone Irisin Is a Critical Regulator of Cognitive Function." Nature Metabolism (First published: August 20, 2021) DOI: 10.1038/s42255-021-00438-z