Inflammation Drives Progression of Alzheimer’s

Interesting, but I bet your doctor won't be following any further experiments on this. Why should she? She is a stroke doctor and needs to know nothing about any form of dementia. Not her job, even though you as her stroke patient will likely get dementia. You're screwed and your doctor is doing nothing.
1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.
2. Then this study came out and seems to have a range from 17-66%. December 2013.
3. A 20% chance in this research.   July 2013.

Inflammation Drives Progression of Alzheimer’s

20 December 2017 Universität Bonn

• Under embargo until 20 December 2017 18:00 GMT

According to a study by scientists of the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn now published in the journal “Nature”, inflammatory mechanisms caused by the brain’s immune system drive the progression of Alzheimer’s disease. These findings, which rely on a series of laboratory experiments, provide new insights into pathogenetic mechanisms that are believed to hold potential for tackling Alzheimer’s before symptoms manifest. The researchers envision that one day this may lead to new ways of treatment. Further institutions both from Europe and the US also contributed to the current results.

Alzheimer’s disease is a devastating neurodegenerative condition ultimately leading to dementia. An effective treatment does not yet exist. The disease is associated with the aberrant aggregation of small proteins called “Amyloid-beta” (Aß) that accumulate in the brain and appear to harm neurons. In recent years, studies revealed that deposits of Aß, known as “plaques”, trigger inflammatory mechanisms by the brain’s innate immune system. However, the precise processes that lead to neurodegeneration and progression of pathology have thus far not been fully understood.

“Deposition and spreading of Aβ pathology likely precede the appearance of clinical symptoms such as memory problems by decades. Therefore, a better understanding of these processes might be a key for novel therapeutic approaches. Such treatments would target Alzheimer’s at an early stage, before cognitive deficits manifest,” says Prof. Michael Heneka, a senior researcher at the DZNE and Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn.

An Inflammatory Cascade

Prof. Heneka, who is also involved in the cluster of excellence “ImmunoSensation” at the University of Bonn, and coworkers have been investigating the role of the brain’s immune response in the progression of Aβ pathology for some time already. Previous work by the group that was published in Nature in 2013, had established that the molecular complex NLRP3, which is 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 is a so-called inflammasome that triggers production of highly pro-inflammatory cytokines. Furthermore, upon activation, NLRP3 forms large signaling complexes with the adapter protein ASC, which are called “ASC specks” that can be released from cells. “The release of ASC specks from activated cells has so far only been documented in macrophages and their relevance in disease processes has so far remained a mystery,” says Prof. Eicke Latz, director of the Institute of Innate Immunity and member of the cluster of excellence “ImmunoSensation” at the University of Bonn

Connection between Inflammation and Neurodegeneration

In the current study, it was demonstrated that ASC specks are also released from activated immune cells in the brain, the “microglia”. Moreover, the findings provide a direct molecular link to classical hallmarks of neurodegeneration. “We found that ASC specks bind to Aß in the extracellular space and promote aggregation of Aß, thus directly linking innate immune activation with the progression of pathology,“ Heneka says.

Novel Approach for Therapy?

This view is supported by a series of experiments in mouse models of Alzheimer’s disease. In these, the researchers investigated the effects of ASC specks and its component, the ACS protein, on the spreading of Aβ deposits in the brain.

“Additionally, analysis of human brain material indicates at several levels that inflammation and Aβ pathology may interact in a similar fashion in humans. Together our findings suggest that brain inflammation is not just a bystander phenomenon, but a strong contributor to disease progression,” Heneka says. “Therefore, targeting this immune response will be a novel treatment modality for Alzheimer’s.”

Attached files

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  Inflammatory proteins (called “ASC specks”, red) within the nucleus of an aggregate of Amyloid-beta peptides (blue). Furthermore, immune cells (green) are shown. Researchers of the DZNE and the University of Bonn report in “Nature” on the role of inflammatory mechanisms in Alzheimer’s disease. Image reconstruction of microscopy imaging data. (c) Dario Tejera/Uni Bonn

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  Prof. Dr. Michael Heneka, a senior researcher at the DZNE and Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn. (c) Photo: UKB/UKOM

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• Full bibliographic information„Microglia-derived ASC specks cross-seed ß-amyloid in Alzheimer’s disease“, Carmen Venegas, Sathish Kumar et al., Nature (2017), DOI: 10.1038/nature25158