2014 Annual Report: 10 Years of Leading Research

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FX11 System’s Effect on Alzheimer’s Disease

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Alzheimer’s disease (AD) results in neuronal death in the brain leading to cognitive problems. The disease is complex and in most cases is thought to have multiple contributing factors. Two systems that have been implicated in AD are blood coagulation and inflammation, since many AD patients have increased blockage of small cerebral blood vessels and increased brain inflammation. In this regard, one arm of the blood coagulation system can promote both the formation of blood clots and the initiation of inflammatory processes. This arm is initiated by activation of the blood protein Factor XII (FXII).
We and others have found that beta-amyloid (Aβ), a small peptide important for the development of AD, can activate FXII. This activation could lead to coagulation and inflammation, both of which could contribute to the subsequent death of brain cells. In fact, we have found that AD patients have more FXII activation in their blood than age-matched, non-demented controls.
These results suggest that the FXII system could be a significant factor in some cases of AD. We will investigate this possibility by studying mouse models of AD in which we can analyze and manipulate FXII and determine the effects on disease progression. If FXII contributes to the pathology of AD, it would open up new strategies for treatment of the disease.