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Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology.
Neurobiol Dis. 2019 04; 124:335-339.ND

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Diouf I
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; CSIRO Health and Biosecurity/Australian E-Health Research Centre, Brisbane, Australia.
Fazlollahi A
CSIRO Health and Biosecurity/Australian E-Health Research Centre, Brisbane, Australia; Cooperative Research Center for Mental Health, Victoria, Australia.
Bush AI
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; Cooperative Research Center for Mental Health, Victoria, Australia.
Ayton S
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; Cooperative Research Center for Mental Health, Victoria, Australia. Electronic address: scott.ayton@florey.edu.au.
Alzheimer's disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainDisease ProgressionFemaleFerritinsHumansMalePrognosis

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30557658

Citation

Diouf, Ibrahima, et al. "Cerebrospinal Fluid Ferritin Levels Predict Brain Hypometabolism in People With Underlying Β-amyloid Pathology." Neurobiology of Disease, vol. 124, 2019, pp. 335-339.
Diouf I, Fazlollahi A, Bush AI, et al. Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology. Neurobiol Dis. 2019;124:335-339.
Diouf, I., Fazlollahi, A., Bush, A. I., & Ayton, S. (2019). Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology. Neurobiology of Disease, 124, 335-339. https://doi.org/10.1016/j.nbd.2018.12.010
Diouf I, et al. Cerebrospinal Fluid Ferritin Levels Predict Brain Hypometabolism in People With Underlying Β-amyloid Pathology. Neurobiol Dis. 2019;124:335-339. PubMed PMID: 30557658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology. AU - Diouf,Ibrahima, AU - Fazlollahi,Amir, AU - Bush,Ashley I, AU - Ayton,Scott, AU - ,, Y1 - 2018/12/14/ PY - 2018/09/03/received PY - 2018/11/07/revised PY - 2018/12/13/accepted PY - 2018/12/18/pubmed PY - 2019/11/30/medline PY - 2018/12/18/entrez KW - Alzheimer's disease KW - Amyloid KW - Biomarker KW - Ferritin KW - Fluorodeoxyglucose KW - Iron KW - Neurodegeneration SP - 335 EP - 339 JF - Neurobiology of disease JO - Neurobiol Dis VL - 124 N2 - 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. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/30557658/Cerebrospinal_fluid_ferritin_levels_predict_brain_hypometabolism_in_people_with_underlying_��_amyloid_pathology_ DB - PRIME DP - Unbound Medicine ER -