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Folia Neuropathologica
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vol. 52

Letter to Editors
Iron-induced fibrin formation may explain vascular pathology in Alzheimer’s disease

Boguslaw Lipinski
Etheresia Pretorius

Folia Neuropathol 2014; 52 (2): 205
Online publish date: 2014/06/30
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To the Editor

In their review article Serý et al. [6] have presented compelling arguments in favour of the role of vascular mechanisms in the development of Alzheimer’s disease (AD). These arguments are in line with a recent series of publications questioning the prevailing concept of amyloid beta-induced neurodegeneration. Already in 2009 Pimplicar published a paper reassessing the amyloid hypothesis in AD [4]. More recently another important paper was published, in which the author has indicated that therapeutic targeting Abeta brain deposits had no significant effect in AD patients [5]. In the last decade of this century, a number of papers appeared that offered alternative explanations of the molecular mechanisms of AD that are related to cardiovascular diseases (CVD). It is well known that the hallmark of CVD is the intravascular formation of persistent fibrin deposits, or thrombi. Under the conditions of normal hemostasis, fibrin is gradually albeit completely removed by a powerful blood fibrinolytic enzyme system. It is known, however, that in the pathologic situations, such as coronary and/or cerebral thrombosis, fibrin clots are refractory to the thrombolytic dissolution [2].
We have recently shown that, when compared to thrombin-generated clots, the iron-induced fibrin has a radically different structure and morphological appearance as documented by scanning electron microscopy [1]. A characteristic feature of this novel form of fibrin (parafibrin) is its complete resistance to the proteolytic degradation. Thus, it may be argued that the formation of parafibrin in the cerebral circulation may be an important factor contributing to AD pathology. Apparently, unfolding of fibrinogen polypeptide chains and its scrambled refolding induced by iron potentiates and/or mimics amyloid deposits in the brain, and in this way contributes to AD pathology. This concept is supported by the findings of Strickland and his group, who have shown that persistent fibrin deposits contribute to neuro-inflammation [3]. In conclusion, we believe that the information presented above supports arguments presented by Serý et al. [6] that deserve further attention.


1. Lipinski B, Pretorius E. Novel pathway of iron-induced blood coagulation: implications for diabetes mellitus and its complications. Pol Arch Med Wewn 2012; 122: 115-122.
2. Lipinski B. Modification of fibrin structure as a possible cause of thrombolytic resistance. J Thromb Thrombolysis 2010; 29: 296-298.
3. Paul J, Strickland S, Melchor JP. Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer’s disease. J Exp Med 2007; 204: 1999-2008.
4. Pimplicar SW. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell Biol 2009; 41: 1261-1268.
5. Reitz C. Alzheimer’s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012; 2012: 3669808.
6. Serý O, Povová J, Míšek I, Pešák L, Janout V. Molecular mechanism of neuropathological changes in Alzheimer’s disease: a review. Folia Neuropathol 2013; 51: 1-9.
Copyright: © 2014 Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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