Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE

• Published in: Nature communications Vol. 6; no. 1; p. 6760
• Main Authors: Ayton, Scott, Faux, Noel G., Bush, Ashley I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/378/2649; 631/45/612/1224; 692/308; 692/699/375/132/1283; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Apolipoproteins E - genetics; Atrophy; Brain - metabolism; Cognition; Cognition Disorders - cerebrospinal fluid; Cognitive ability; Cohort Studies; Databases, Factual; Female; Ferritins - cerebrospinal fluid; Gene Expression Regulation; Genotype; Humanities and Social Sciences; Humans; Iron; Iron - cerebrospinal fluid; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; multidisciplinary; Risk Factors; Science; Science (multidisciplinary); Treatment Outcome
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7760

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. Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.