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The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin.
Neurobiol Dis 2015; 81:49-65ND

Abstract

The dysregulation of iron metabolism in Alzheimer's disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer's disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer's disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer's disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer's disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer's pathology.

Authors+Show Affiliations

Department of Neurosurgery, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA; Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA.Department of Neurosurgery, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA.Department of Neurosurgery, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA; Department of Radiology, The Center for NMR Research, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA. Electronic address: markmeadowcroft@psu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26303889

Citation

Peters, Douglas G., et al. "The Relationship Between Iron Dyshomeostasis and Amyloidogenesis in Alzheimer's Disease: Two Sides of the Same Coin." Neurobiology of Disease, vol. 81, 2015, pp. 49-65.
Peters DG, Connor JR, Meadowcroft MD. The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. Neurobiol Dis. 2015;81:49-65.
Peters, D. G., Connor, J. R., & Meadowcroft, M. D. (2015). The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. Neurobiology of Disease, 81, pp. 49-65. doi:10.1016/j.nbd.2015.08.007.
Peters DG, Connor JR, Meadowcroft MD. The Relationship Between Iron Dyshomeostasis and Amyloidogenesis in Alzheimer's Disease: Two Sides of the Same Coin. Neurobiol Dis. 2015;81:49-65. PubMed PMID: 26303889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. AU - Peters,Douglas G, AU - Connor,James R, AU - Meadowcroft,Mark D, Y1 - 2015/08/22/ PY - 2015/02/23/received PY - 2015/08/04/revised PY - 2015/08/12/accepted PY - 2015/8/26/entrez PY - 2015/8/26/pubmed PY - 2016/8/23/medline KW - AD KW - Alzheimer's disease KW - Amyloidogenesis KW - Beta-amyloid KW - Dyshomeostasis KW - Iron KW - Metallosis KW - Pathology SP - 49 EP - 65 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 81 N2 - The dysregulation of iron metabolism in Alzheimer's disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer's disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer's disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer's disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer's disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer's pathology. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/26303889/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(15)30028-0 DB - PRIME DP - Unbound Medicine ER -