title: Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.
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-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.
authors.affiliation: Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Scott
authors.identifier: 0000000234792427
authors.initials: S
authors.lastname: Ayton
authors.affiliation: 1] Bioinformatics Core, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia.
authors.forename: Noel G
authors.identifier: 0000000345948818
authors.initials: NG
authors.lastname: Faux
authors.affiliation: 1] Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia.
authors.forename: Ashley I
authors.identifier: 0000000182599069
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy; D001921:Brain / Q000378:metabolism; D003071:Cognition; D003072:Cognition Disorders / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005293:Ferritins / Q000134:cerebrospinal fluid*; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007501:Iron / Q000134:cerebrospinal fluid; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001057:Apolipoproteins E; D005293:Ferritins; D007501:Iron