Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology
Neurobiology of Disease
Volume 124, April 2019, Pages 335-339
Ibrahima Diouf, Amir Fazlollahi, Ashley I.Bush, Scott Ayton
for the Alzheimer's disease Neuroimaging Initiative1

https://doi.org/10.1016/j.nbd.2018.12.010

Highlights
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CSF ferritin predicts future brain hypometabolism in pre-clinical Alzheimer's disease.

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CSF ferritin adds prognostic value to other Alzheimer's biomarkers: CSF t-tau and Aβ42.

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Evidence that brain iron mediates neurodegeneration in prodromal Alzheimer's disease.

Abstract
β-Amyloid pathology is elevated in ~30% of cognitively normal people over 65, and is associated with accelerated neurodegeneration in the pre-clinical stages of Alzheimer's disease. Recent findings reveal that brain iron might also act to propel neurodegeneration in people with underlying amyloid pathology. Here, repeated PET scans of fluorodeoxyglucose (FDG) were used as a biomarker for brain hypometabolism and a downstream biomarker of neurodegeneration to investigate whether levels of ferritin in the cerebrospinal fluid (CSF; a reporter of brain iron load) are associated with prodromal disease progression of people with high β-amyloid pathology determined by established cut-off values in CSF t-tau/Aβ42 ratio. Nineteen cognitively normal participants with low t-tau/Aβ42, and 71 participants with high t-tau/Aβ42 who were cognitively normal or had mild cognitive impairment were included as participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. These subjects had repeated FDG-PET scans at 6-month intervals for 2 years, and yearly intervals for up to a further 3 years. In mixed-effects linear models of FDG signal, baseline CSF ferritin was associated with an accelerated decline in FDG PET in high t-tau/Aβ42 participants (β[SE] = −0.066 [0.017]; P = .0002), but not in people with low t-tau/Aβ42 (−0.029 [0.049]; P = .554). These data implicate iron as a contributing factor to neurodegeneration associated with β-amyloid pathology, and highlight CSF ferritin as a complementary prognostic biomarker to the t-tau/Aβ42 ratio that predicts near-term risk for disease progression.

Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

© 2018 Elsevier Inc. All rights reserved.

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