Heme Deficiency in Alzheimer’s Disease: A Possible  Connection to
Porphyria

Dwyer, Barney E.; Stone, Meghan L.; Zhu, Xiongwei; Perry, George; Smith, Mark A.

doi:https://doi.org/10.1155/JBB/2006/24038

BioMed Research International

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Neurodegenerative Diseases: Mechanisms and Therapies

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Research Article | Open Access

Volume 2006 | Article ID 024038 | https://doi.org/10.1155/JBB/2006/24038

Heme Deficiency in Alzheimer’s Disease: A Possible Connection to Porphyria

Barney E. Dwyer,^1,2Meghan L. Stone,¹Xiongwei Zhu,³George Perry,³and Mark A. Smith³

Received01 Dec 2005

Revised30 Mar 2006

Accepted05 Apr 2006

Published25 Jun 2006

Abstract

Mechanisms that cause Alzheimer’s disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity of genes encoding enzymes of the heme biosynthesis pathway to genetic loci linked to sporadic, late-onset AD. In addition, we suggest that identification of individuals carrying the genetic trait for acute porphyria may provide a unique resource for investigating AD pathogenesis and inform treatment and management decisions.

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Copyright © 2006 Barney E. Dwyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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