The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

Douglas G. Peters, James Connor, Mark Meadowcroft

Research output: Contribution to journalReview article

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)49-65
Number of pages17
JournalNeurobiology of Disease
Volume81
DOIs
StatePublished - Sep 1 2015

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Alzheimer Disease
Iron
Amyloid Plaques
Amyloid
Brain
Homeostasis
Pathology
Poisons
Amyloid beta-Peptides
Genetic Polymorphisms
Disease Progression
Enzymes

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

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The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease : Two sides of the same coin. / Peters, Douglas G.; Connor, James; Meadowcroft, Mark.

In: Neurobiology of Disease, Vol. 81, 01.09.2015, p. 49-65.

Research output: Contribution to journalReview article

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