Changes in blood flow and coagulation may contribute to Alzheimer's pathology
There are many proteins and enzymes that are involved with the coagulation process in blood, which evolved to react to injury and invasion by various microorganisms. One of these is factor XII, which sets off an important cascade - triggering an inflammatory, coagulation response. New research at the Rockefeller University has determined that this same cascade can be activated by the presence of beta amyloid, which is strongly implicated in Alzheimer's progression, whether or not it is a cause or response to another underlying trigger.
"There's a lot of evidence that exercise, which helps keep your blood vessels healthy and blood flow consistent, can be protective against AD. In addition, we know that diseases that compromise the vascular system, like diabetes, put people at higher risk"
In typical Alzheimer's patients raised beta amyloid levels emerge first, and vascular changes follow. These changes can take many years to create any observable cognitive deficits. It's a disease that is years in the making.
Testing the importance of factor XII
After noting this link, researchers blocked factor XII expression in mice to test whether it affected a model of Alzheimer's. Indeed, blocking factor XII lowered brain inflammation, which is a critical marker of Alzheimer's risk and progression. Cognitive behaviour and memory also appeared to be boosted by factor XII inhibition. While those mice with Alzheimer's and knocked down factor XII performed much better than those with normal expression of the protein, they were still behind healthy mice. This suggests that it may be a contributory factor, but that it's certainly not the whole picture.
However, while the research points to vascular impairment as an important factor in the disease, it also raises additional questions. Again we must ask what causes a rise in beta amyloid and a spike in inflammatory processes. Previous work has suggested this may be due to a huge range of things, including possible microbial burden. We will have to await further research as we narrow down the collective causes.
"Our work contributes to the increasing evidence that vascular abnormalities are playing an important role in cognitive decline and inflammation in some AD patients. The hope is that defining the vascular mechanisms involved will allow for better diagnosis and eventually new treatments. Each step forward is a step closer to understanding this terrible disease"
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