Amyloid hypothesis of
Alzheimer's disease (AD) has recently been challenged by the increasing evidence for the role of vascular and
hemostatic components that impair
oxygen delivery to the brain. One such component is
fibrin clots, which, when they become resistant to thrombolysis, can cause chronic
inflammation. It is not known, however, why some cerebral thrombi are resistant to the fibrinolytic degradation, whereas
fibrin clots formed at the site of vessel wall
injuries are completely, although gradually, removed to ensure proper wound healing. This phenomenon can now be explained in terms of the
iron-induced
free radicals that generate
fibrin-like
polymers remarkably resistant to the proteolytic degradation. It should be noted that similar insoluble deposits are present in AD brains in the form of aggregates with Abeta
peptides that are resistant to fibrinolytic degradation. In addition,
iron-induced
fibrin fibers can irreversibly trap red blood cells (RBCs) and in this way obstruct
oxygen delivery to the brain and induce chronic
hypoxia that may contribute to AD. The RBC-
fibrin aggregates can be disaggregated by
magnesium ions and can also be prevented by certain
polyphenols that are known to have beneficial effects in AD. In conclusion, we argue that AD can be prevented by: (1) limiting the dietary supply of trivalent
iron contained in red and processed meat; (2) increasing the intake of
chlorophyll-derived
magnesium; and (3) consumption of foods rich in polyphenolic substances and certain aliphatic and aromatic unsaturated compounds. These dietary components are present in the
Mediterranean diet known to be associated with the lower incidence of AD and other degenerative diseases.