Alzheimer's Neuroinflammation and Neurovascular Damage Enhanced by Fibrin

The primary cause and clinical manifestation of Alzheimer's Disease (AD) is currently understood to be the beta-amyloid plaques that are so lethal to the nerve cells they surround. Additionally, a secondary event that may be just as detrimantal in the AD pathology is the tau protein neurofibrillatory tangles that are present in this disease. Now, looking at more inflammatory processes, specifically those linked to neurovascular damage, may allow even further understanding and treatment of AD by minimizing these acceleratory events.
In the paper "Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer's disease", Paul et al show very thorough evidence that fibrin plays an active part in the disease and its progression. Something that is crucial to understand about this horrible disease that is demonstrated in this paper and really focused on in many others is that it is a "downward spiral" process where the events that are involved in the pathology are all rapidly increasing the disease as they enhance each other's potent effects. For example, it is understood that it is beneficial to the brain cells to use them and this promotes their own health; but, with AD, brain cells are degrading and therefore less used which only propogates their deterioration. Inflammatory events also often work this way, and certainly in AD this not only adds to the pathology, but maybe, better said, multiplies or exponentializes it. Fibrin, here, is shown to be quite active in this, especially as an indicator and even a cause of vascular damage in the brain, which can dramatically speed up the devastating destruction of the brain tissue, allowing more proteins and harmful products through the blood brain barrier and causing more cell loss. This paper was especially impressive because of the thorough degree to which it investigated its hypothesis. Namely, it not only looked at a mouse model with higher fibrinogen, the precursor to fibrin, but also one with affected plasminogen levels, which is the precursor to plasmin which promotes fibrinolysis, or the breakdown of fibrin. The model used both genetic and pharmacologic approaches to assay whether or not there was real substance to its hypothesis and went far beyond the mere few angles that could have been used to check this out.
I would also like to point out that this month's National Geographic (Nov 2007) has its cover story on "Memory - Why We Remember, Why We Forget" and really highlights some of the things that are crucial to look at when delving into anything related to memory and the brain. Plus, it has some cool perspectives from some very exceptional individuals on both ends of the spectrum related to this subject.