title: The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin.
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: 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.
authors: Douglas G
authors: DG
authors: Peters
authors: Department of Neurosurgery, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA.
authors: James R
authors: JR
authors: Connor
authors: 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.
authors: Mark D
authors: MD
authors: Meadowcroft
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000209:etiology / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D007501:Iron
keywords: AD; Alzheimer's disease; Amyloidogenesis; Beta-amyloid; Dyshomeostasis; Iron; Metallosis; Pathology