TY - JOUR
T1 - Iron, zinc and copper in the Alzheimer's disease brain
T2 - A quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion
AU - Schrag, Matthew
AU - Mueller, Claudius
AU - Oyoyo, Udochukwu
AU - Smith, Mark A.
AU - Kirsch, Wolff M.
N1 - Funding Information:
This material was made available to Mark Lovell and Elizabeth Head at the Sanders Brown Center of Aging at the University of Kentucky prior to submission. We are grateful that they took the time to review this data and the graciousness with which they have treated us. This work was funded in part by the National Institutes of Health ( AG20948 ). The authors are aware of no real or potential conflicts of interests related to this material.
PY - 2011/8
Y1 - 2011/8
N2 - Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer's disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p< 0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD.
AB - Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer's disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p< 0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD.
KW - Chelation
KW - Citation bias
KW - Meta-analysis
KW - Publication bias
KW - Transition metals
UR - http://www.scopus.com/inward/record.url?scp=79959395494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959395494&partnerID=8YFLogxK
U2 - 10.1016/j.pneurobio.2011.05.001
DO - 10.1016/j.pneurobio.2011.05.001
M3 - Review article
C2 - 21600264
SN - 0301-0082
VL - 94
SP - 296
EP - 306
JO - Progress in Neurobiology
JF - Progress in Neurobiology
IS - 3
ER -