Abstract:
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 vesselwall 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 thatAD 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.
