In a special issue of the Journal of Alzheimer’s Disease, guest editors Andrei C. Miu and Oana Benga have gathered 14 insightful articles that explore the roles that metal species play in Alzheimer’s Disease.
Alzheimer’s disease (AD) is a
neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. It is the most common type of dementia. Alzheimer's disease has been identified as a protein misfolding disease due to the accumulation of abnormally folded amyloid beta protein in the brains of AD patients. Its causes are still largely unknown but various metals have been implicated as possible contributors to the development of AD.
Figure: Prevalence of Alzheimer disease in different age groups
In a special double
issue of the Journal of Alzheimer’s Disease
November 2006, guest editors Andrei C. Miu and Oana Benga have brought
together 14 articles exploring the roles that metal species play
in the biochemistry and physiology of AD. These articles cover six
major categories: Comprehensive historical reviews, methodological
perspectives, a topical review, integrative genetic and epigenetic
reports, a review of risk factors and a “benchmark to clinical” review.
guest editors Andrei C. Miu and Oana Benga: “We are grateful to the
authors who accepted our challenge and who have shown that
metallobiologists working in AD research have been less fascinated with
describing end-stage pathognomonic lesions, and more concerned with
identifying risk and aggravating factors that might help us better
predict, diagnose and hopefully prevent AD in the future.”
The content of the special issue:
Savory, Mary M. Herman and Othman Ghribi review the four-decades-old
controversy about aluminum neurotoxicity, examining data on the
possible cellular mechanisms underlying aluminum neurotoxicity and
potential neuroprotective strategies against aluminum toxicity. In the
next review, Paul A. Adlard and Ashley I. Bush discuss how metal ions
such as zinc and copper can potentiate Alzheimer’s disease by
participating in the aggregation of normal cellular proteins and in the
generation of reactive oxygen species. In the third review article,
Arezoo Campbell focuses on how aluminum and copper can initiate or
propagate an inflammatory response in the aging brain. Christopher
Exley reviews in-vitro studies of metals found in plaque cores in AD
brains and concludes that aluminum and iron could cause oxidative
damage but copper and zinc likely do not. In the final review article,
Andrei C. Miu and Oana Benga recount the long history of aluminum’s
hypothetical role in AD. They extensively discuss several lines of
evidence for involvement of aluminum as a secondary aggravating factor
or risk factor and argue that further studies are warranted.
Platt discusses the methodologies that have been used to identify
Alzheimer- and dementia-related targets for exogenous toxins. She
explains how neuronal function can be assessed experimentally, based on
the evidence obtained for the neurotoxin aluminum. In the second
article on methods, Joanna Collingwood and Jon Dobson write about
recent approaches to locate and identify iron compounds in
neurodegenerative tissue. In addition to complementary techniques that
allow them to quantify and identify iron compounds using magnetometry,
extraction and electron microscopy, they utilize a powerful combined
mapping/characterization approach with synchrotron X-rays.
movement of metals across the blood-brain barrier is reviewed by Robert
A. Yokel. A number of transporters are described that could mediate
metal transport into and out of the brain. He reviews the role of these
transporters in moving aluminum, manganese, iron and other metals
across the blood-brain barrier.
Hani Atamna has developed a novel
model of amyloid-beta induced heme-deficiency that could account for
neurodegeneration in AD patients. He reviews the genetic, nutritional
and toxicological factors that influence heme metabolism and their
relevance to AD. James R. Connor and Sang Y. Lee discuss genetic
mutations in the HFE gene that can affect iron balance in the brain,
potentially leading to the generation of reactive oxygen and oxidative
damage. In a study of the presenilins (PS), Nazneen N. Dewji discusses
how these proteins can trigger a cascade of processes that lead to
amyloid-beta production, leading to AD. He reviews the structures of
the PS proteins that can support the model of a surface reaction
between two nearby brain cells. Iftach Dolev and Daniel M. Michaelson
write about the apoE4 isoform of apolipoprotein E. Their study of the
nucleation, growth and reversibility of amyloid-beta deposition in mice
should shed new light on this genetic risk factor for AD.
Solfrizzi and co-authors review the possible role of macronutrients and
the basic elements of carbohydrates, proteins, and fat in the
development of AD. They suggest that healthy diets, antioxidant
supplements, and the prevention of nutritional deficiencies or exposure
to foods and water with high content of metals could be considered the
first line of defense against the development and progression of
In the final article, Jose L. Domingo focuses
on the role of aluminum and metals such as copper and zinc in AD, as
well as on metal chelator therapy as a potential treatment for AD. The
effects of aluminum, copper and zinc chelating agents on amyloid-beta
plaques are reviewed.
The Special Issue: Metals in Alzheimer's Disease edited by Andrei Miu and Oana Benga; Program of Cognitive Neuroscience, Department of Psychology, Babes¸-Bolyai University, Cluj-Napoca, CJ, Romania, J. Alzheimer Dis., 10/2-3 (2006)
Andrei C. Miu and Oana Benga, Foreword: Metals in Alzheimer's Disease, J. Alzheimer Dis., 10/2-3 (2006) 133. John Savory, Mary M. Herman, Othman Ghribi, Mechanisms of aluminum-induced neurodegeneration in animals: implications for Alzheimer's disease, J. Alzheimer Dis., 10/2-3 (2006) 135-144. Paul A. Adlard, Ashley I. Bush, Metals and Alzheimer’s disease, J. Alzheimer Dis., 10/2-3 (2006) 145-163.
Arezoo Campbell, The role of aluminum and copper on neuroinflammation and Alzheimer’s disease, J. Alzheimer Dis., 10/2-3 (2006) 165-172. Christopher Exley, Aluminium
and iron, but neither copper nor zinc, are key to the precipitation of
ß-sheets of Aß42 in senile plaque cores in Alzheimer’s disease, J. Alzheimer Dis., 10/2-3 (2006) 173-177. Andrei C. Miu and Oana Benga, Aluminum and Alzheimer's disease: a new look, J. Alzheimer Dis., 10/2-3 (2006) 179-201. Bettina Platt, Experimental approaches to assess metallotoxicity and ageing in models of Alzheimer’s disease, J. Alzheimer Dis., 10/2-3 (2006) 203-213. Joanna Collingwood and Jon Dobson, Mapping and characterization of iron compounds in Alzheimer’s tissue, J. Alzheimer Dis., 10/2-3 (2006) 215-222. Robert A. Yokel, Blood-Brain
Barrier Flux of Aluminum, Manganese, Iron and Other Metals Suspected to
Contribute to Metal-Induced Neurodegeneration, J. Alzheimer Dis., 10/2-3 (2006) 223-253. Hani Atamna, Heme Binding to Amyloid-ß Peptide: A Mechanism for Neuroprotection from Alzheimer’s Disease, J. Alzheimer Dis., 10/2-3 (2006) 255-266. James R. Connor and Sang Y. Lee, HFE Mutations and Alzheimer’s Disease, J. Alzheimer Dis., 10/2-3 (2006) 267-276. Nazneen N. Dewji, Presenilin structure in mechanisms leading to Alzheimer’s disease, J. Alzheimer Dis., 10/2-3 (2006) 277-290. Iftach Dolev, Daniel M. Michaelson, The Nucleation Growth and Reversibility of Amyloid-ß Deposition in vivo, J. Alzheimer Dis., 10/2-3 (2006) 291-301. Vincenzo
Solfrizzi, Anna Maria Colacicco, Alessia D’Introno, Cristiano Capurso,
Angelo Del Parigi, Sabrina A. Capurso, Francesco Torres, Antonio
Capurso, Francesco Panza, Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia, J. Alzheimer Dis., 10/2-3 (2006) 303-330.
Jose L. Domingo, Aluminum and other metals in Alzheimer’s disease: A review of potential therapy with chelating agents, J. Alzheimer Dis., 10/2-3 (2006) 331-341.
E. Gauthier, I. Fortier, F. Courchesne, P. Pepin, J. Mortimer, D. Gaovreau, Aluminium forms in drinking waters and risk for Alzheimer's Disease, Environ. Res. (U.S.A), 84/3 (2000) 234-246. doi:10.1006/enrs.2000.4101
Andreas Prange, Dirk Schaumlöffel, Peter Brätter, Andrea-Nicole Richarz, Christian Wolf, Species analysis of metallothionein isoforms in human brain cytochrome by use of capillary electrophoresis hyphenated to inductively coupled plasma-sector field mass spectrometry, Fresenius J. Anal. Chem., 371/6 (2001) 764-774.
J.S. Becker, M. Zoriy, C. Pickhardt, M. Przybylski, Johanna Sabine Becker, Investigation of Cu-, Zn- and Fe-containing human brain proteins using isotopic-enriched tracers by LA-ICP-MS and MALDI-FT-ICR-MS, Int. J. Mass Spectrom., 242/2-3 (2005) 135-144. doi: 10.1016/j.ijms.2004.10.027
Ari Ide-Ektessabi, Mariona Rabionet, The Role of Trace Metallic Elements in Neurodegenerative Disorders: Quantitative Analysis Using XRF and XANES Spectroscopy, Anal. Sci., 21/7 (2005) 885. DOI: 10.2116/analsci.21.885
Ayesha Khan, Jon P. Dobson, Christopher Exley, Redox cycling of iron by Aß42, Free Radic. Biol. Med., 40/4 (2006) 557-569. doi: 10.1016/j.freeradbiomed.2005.09.013
last time modified: November 26, 2008