Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE
Authors
Scott Ayton, University of Melbourne
Noel G. Faux, University of Melbourne
Ashley I. Bush, University of Melbourne
Michael W. Weiner, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
William Jagust, University of California, Berkeley
John Q. Trojanowki, University of Pennsylvania
Arthur W. Toga, USC
Laurel Beckett, University of California, Davis
Robert C. Green, Brigham and Women's Hospital
Andrew J. Saykin, Indiana University Bloomington
John Morris, Washington University in St. Louis
Leslie M. Shaw, University of Pennsylvania
Zaven Khachaturian, University of California, San Diego
Greg Sorensen, Siemens AG
Lew Kuller, University of Pittsburgh
Marc Raichle, Washington University in St. Louis
Steven Paul, Cornell University
Peter Davies, Albert Einstein College of Medicine of Yeshiva University
Howard Fillit, AD Drug Discovery Foundation
Franz Hefti, Acumen Pharmaceuticals
Davie Holtzman, Washington University in St. Louis
M. Marcel Mesulam, Northwestern University
William Potter, National Institute of Mental Health (NIMH)
Peter Snyder, Brown University
Adam Schwartz, Eli Lilly
Tom Montine, University of Washington
Ronald G. Thomas, University of California, San Diego
Michael Donohue, University of California, San Diego
Sarah Walter, University of California, San Diego
Publication Date
5-19-2015
Journal
Nature Communications
URL with Digital Object Identifier
10.1038/ncomms7760
Abstract
Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.
