Alzheimer Hastalığında Demirin Rolü

Year 2020, Volume: 42 Issue: 2, 254 - 257, 17.03.2020

Mevra Al Cansu Kılıç Fatma Sultan Kılıç

Abstract

Alzheimer hastalığı
(AH), demans tablosunun en sık nedeni (%60-80) olan kronik nörodejeneratif bir
hastalıktır. Her yıl tüm dünyada 4.6 milyon yeni AH olgusu geliştiği tahmin
edilmektedir. Hastalığın görülme riski yaşa bağlı olarak logaritmik
biçimde artar. Yaşı 60-65 arasında olan popülasyonda görülme sıklığı
yaklaşık olarak %0.1 iken 85 yaşın üzerinde görülme sıklığı %47’ye kadar
çıkar. Tanı konulmasında özel bir belirteç olmaması, bilim adamlarını farklı
tanı yolları aramaya itmiştir. Bu nedenle yapılan incelemelerde serum demiri yüksek
ve transferrin saturasyonu düşük erişkinlerde nörolojik demansiyel hastalıkların
başlayabileceği ortalama 6 ay öncesinden öngörülebilmektedir. Serum demiri yüksekliği
beyin dokusunda da demir yüksekliğine yol açabilmektedir. Bu süreç, AH’de erken
tanı açısından faydalı olacaktır.

Keywords

Alzheimer hastalığı

The Role of Iron in Alzheimer’s Disease

Abstract

Alzheimer’s
disease is a chronical neurodegenerative disease and it is the most commanly
seen (%60-80) reason of dementia.  It is
predicted that every year 4.6 million new cases occur around the world. The
risk increases logarithmically depending on age. The incidence is %0.1 between
ages 60-65  while it is %47 over age 85.
Scientists are researching on  different
diagnostic methods since there isn’t a certain indicator for diagnosis.
Research showed that blood iron levels increasing and transferrin saturation
starts decreasing 6 months before the neurogical demential diseases occur. High
iron levels in blood serum causes high iron levels in the brain tissue. This
process will be useful for early diagnosis of AD.

Keywords

Alzheimer Disease and blood iron levels

References

• 1. Sakurai H, Hanyu H, Iwamoto T. Toward defining the preclinical stages of Alzheimer’s disease. J Tokyo Med Univ. 2012;70(3):332–3.
• 2. Sepulcre J, Grothe MJ, d’Oleire Uquillas F, Ortiz-Terán L, Diez I, Yang H-S, et al. Neurogenetic contributions to amyloid beta and tau spreading in the human cortex. Nat Med. 2018;24(12):1910–8.
• 3. Crichton R. Inorganic Biochemistry of Iron Metabolism: From Molecular Mechanisms to Clinical Consequences. Chichester: John Wiley & Sons; 2009. 461 p.
• 4. Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014 Oct;13(10):1045–60.
• 5. Aoki S, Okada Y, Nishimura K, Barkovich AJ, Kjos BO, Brasch RC, et al. Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. Radiology. 1989 Aug;172(2):381–5.
• 6. Bartzokis G, Beckson M, Hance DB, Marx P, Foster JA, Marder SR. MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imaging. 1997;15(1):29–35. 7. Altamura S, Muckenthaler MU. Iron toxicity in diseases of aging: Alzheimer’s disease, Parkinson’s disease and atherosclerosis. J Alzheimer’s Dis. 2009;16(4):879–95.
• 8. Roberts BR, Ryan TM, Bush AI, Masters CL, Duce JA. The role of metallobiology and amyloid-β peptides in Alzheimer’s disease. J Neurochem. 2012;120(SUPPL. 1):149–66.
• 9. Good PF, Perl DP, Bierer LM, Schmeidler J. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol. 1992 Mar;31(3):286–92.
• 10. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer’s disease. J Neurosci Res. 1992 Feb;31(2):327–35.
• 11. Smith MA, Harris PL, Sayre LM, Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9866–8.
• 12. Yamamoto A, Shin R-W, Hasegawa K, Naiki H, Sato H, Yoshimasu F, et al. Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J Neurochem. 2002 Sep;82(5):1137–47.
• 13. Huat TJ, Camats-perna J, Newcombe EA, Valmas N, Kitazawa M, Medeiros R. Metal Toxicity Links to Alzheimer’s Disease and Neuroinflammation. J Mol Biol. 2019;(xxxx):1–26.
• 14. Silvestri L, Camaschella C. A potential pathogenetic role of iron in Alzheimer’s disease. J Cell Mol Med. 2008;12(5A):1548–50.
• 15. Eder PS, Leiter L, Tanzi RE, Greig NH, Bush AI, Giordano T, et al. An Iron-responsive Element Type II in the 5′-Untranslated Region of the Alzheimer’s Amyloid Precursor Protein Transcript. J Biol Chem. 2002;277(47):45518–28.
• 16. Tsokos M, Switzer R, Grinberg A, Love P, Tresser N, Rouault TA, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27(2):209–14.
• 17. Rouault T, Klausner R. Regulation of iron metabolism in eukaryotes. Curr Top Cell Regul. 1997;35:1–19.
• 18. Hentze MW, Kühn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175–82.