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29 - 03 - 2017

Alzheimer’s: the importance of the vascular system found in mice

Cardiovascular diseases are recognized as a risk and aggravating factor of Alzheimer’s disease. But the underlying mechanism hasn’t been clearly established. American researchers have made a discovery in mice. Explanations. 

Alzheimer’s: the importance of the vascular system found in mice

For several years now, scientific studies have shown a correlation between cardiovascular diseases and Alzheimer's disease. Diabetes, cholesterol and hypertension, all seem to be risk factors for this neurodegenerative disease, and may even aggravate its symptoms. According to the INSERM, these cardiovascular risk factors could be linked to an "altered performance of the cerebral vascular system", which would "aggravate the pathological process".

Alzheimer's disease is characterized by two types of brain lesions: amyloid plaques (or senile plaques) - deposits associated with the abnormal accumulation of amyloid beta protein outside the neurons - and neurofibrillary degenerations - linked to the aggregation of the tau protein, in the form of filaments within the neurons.


Amyloid beta activates a blood plasma protein


Researchers at the University of Rockefeller (New York, USA) have identified a factor that at least partly explains this link between cardiovascular and Alzheimer's diseases. It is a plasma protein, called Factor XII, which is part of an enzymes cascade that induces blood coagulation and inflammation. Previous work has shown that this cascade can be activated by the beta amyloid protein, the very one that accumulates in the brains of patients with Alzheimer's disease.




Effect on inflammation and cognition


To prove that the factor XII plays a role in Alzheimer’s disease, a team sought to inactivate this plasma protein. To do this, scientists used a mouse model, as such experiments can’ be done in vitro or in humans. To block the activation of factor XII, the team used a molecule that prevented the gene from producing this protein. Result: Alzheimer mice with a blocked factor XII showed less cerebral inflammation than untreated Alzheimer mice, and their brain resembled that of healthy, unaffected mice without inflammation. Cognitive functions of Alzheimer's mice with a blocked factor XII showed better cognitive outcomes than the others, but did not match those of healthy mice.

"Our work helps prove that vascular abnormalities play an important role in the cognitive decline and inflammation seen in some patients with Alzheimer's disease," concluded Sidney Strickland, co-author of this study, which appeared in The Journal Blood. "Hopefully the description of the vascular mechanisms involved will allow a better diagnosis and one day maybe new treatments. Every step forward is one step closer to understanding this terrible disease. "



Hélène Bour



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