Ferric cycle activity and Alzheimer disease

Barney E. Dwyer, Atsushi Takeda, Xiongwei Zhu, George Perry, Mark A. Smith

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)

Abstract

Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.

Original languageEnglish
Pages (from-to)261-267
Number of pages7
JournalCurrent Neurovascular Research
Volume2
Issue number3
DOIs
Publication statusPublished - 2005 Jul 1

Keywords

  • Alzheimer disease
  • Ferric cycle
  • Heme
  • Iron homeostasis
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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