Microglial Neuroinflammation as a Cause of Tau Aggregation

Chronic inflammation in the brain is an important aspect of all neurodegenerative conditions. In particular, as discussed in this open access paper, there is good evidence for inflammatory and dysfunctional (and senescent) microglia to drive the tau protein aggregation characteristic of late stage Alzheimer's disease. It remains to be seen as to how the research community will build on past years of research on this topic to develop therapies, but one of the best near term possibilities is the use of senolytic therapies such as the dasatinib and quercetin combination to selectively destroy senescent microglia in the aging brain.

Histopathological features of Alzheimer's disease (AD) are extracellular amyloid-β (Aβ) plaques and intracellular aggregation of hyperphosphorylated tau protein in a form of neurofibrillary tangles (NFTs). The disease is also characterized by loss of neurons and synapses and elevated levels of inflammatory factors. Neuroinflammation occurs in many neurodegenerative diseases, including AD. Several studies confirmed elevated levels of pro-inflammatory cytokines and stronger microglial activation during disease progression. Activated microglia have been found near NFT-bearing neurons. There is also a better correlation between numbers of activated microglia and NFT than between microglial cells' activation and amyloid plaques distribution.

Uncontrolled microglial response in the brain contributes to the progression of many neurodegenerative diseases and several lines of evidence suggest that inflammation may even precede the development of tau pathology in AD. Exosomes could be an important link between tau propagation and microglial activation. Reduction of microglial cells number and exosome synthesis inhibition reduces tau propagation. Further, phagocytosed tau seeds induce inflammasome activation inside microglia causing an overactive microglia state. That could be one of the mechanisms that promote the constant inflammatory response in AD.

Link: https://doi.org/10.3389/fnagi.2019.00271

Comments

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.