Inflammation Plays a Role in Alzheimer’s disease

Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn have shown that inflammatory mechanisms from the brain’s immune system drive the progression of Alzheimer’s disease. The research provides new insights into the pathogenetic mechanisms that may hold the potential for preventing Alzheimer’s disease before symptoms show up.

Alzheimer’s disease is a neurodegenerative condition that eventually leads to dementia. The disease is associated with the aggregation of small proteins called “Amyloid-beta” (Abeta), known as “plaques,” that accumulate in the brain and are believed to harm neurons. Prior studies have shown deposits of Abeta trigger inflammatory mechanisms by the brain’s immune system. Researchers believe that deposition and spreading of Abeta likely precede any clinical symptoms by decades. Even so researchers do not fully understand the processes responsible and thus believe by doing so that effective treatments to target Alzheimer’s disease at an early stage may be possible.

The researchers have been investigating the role of the brain’s immune response in the progression of Abeta pathology for many years. The group previously published work in Nature in 2013, that established that the molecular complex NLRP3, an innate immune sensor, is activated in brains of Alzheimer’s patients and contributes to the pathogenesis of Alzheimer’s in the murine model. NLRP3 triggers production of highly pro-inflammatory cytokines. NLRP3 when activated forms large signaling complexes with the adapter protein ASC which are released from cells, called “ASC specks.” The release of ASC specks from activated cells has been documented in macrophages.

In the current study, it was demonstrated that ASC specks are also released from activated immune cells in the brain, the “microglia.” The results also provide a direct molecular link to classical hallmarks of neurodegeneration. The researchers found that ASC specks bind to Abeta in the extracellular space and promote aggregation of Abeta, thus linking immune activation with disease progression. This was shown by experiments in mouse models of Alzheimer’s disease. In the experiments, the researchers investigated the effects of ASC specks and the ACS protein on the spreading of Abeta deposits in the brain. Analysis of human brain material indicates at several levels that inflammation and Abeta pathology may interact in humans in a similar way as shown in the mouse model studies. The findings support that brain inflammation contributes to Alzheimer’s disease progression. The researchers believe that targeting the immune response that causes the inflammation will be a possibly to treat Alzheimer’s disease.

For additional ways that may help treat Alzhiemer’s disease see the prior post and

Source: Carmen Venegas, and et al., Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease, Nature, 2017.

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