Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology
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 amylo...
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doaj-795dc037bdac4451962eb53cb1f7d6532021-03-22T12:47:21ZengElsevierNeurobiology of Disease1095-953X2019-04-01124335339Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathologyIbrahima Diouf0Amir Fazlollahi1Ashley I. Bush2Scott Ayton3Melbourne 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, AustraliaCSIRO Health and Biosecurity/Australian E-Health Research Centre, Brisbane, Australia; Cooperative Research Center for Mental Health, Victoria, AustraliaMelbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; Cooperative Research Center for Mental Health, Victoria, AustraliaMelbourne 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; Corresponding author at: The Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, Victoria 3052, Australia.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.http://www.sciencedirect.com/science/article/pii/S0969996118305369Alzheimer's diseaseIronAmyloidBiomarkerNeurodegenerationFerritin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ibrahima Diouf Amir Fazlollahi Ashley I. Bush Scott Ayton |
spellingShingle |
Ibrahima Diouf Amir Fazlollahi Ashley I. Bush Scott Ayton Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology Neurobiology of Disease Alzheimer's disease Iron Amyloid Biomarker Neurodegeneration Ferritin |
author_facet |
Ibrahima Diouf Amir Fazlollahi Ashley I. Bush Scott Ayton |
author_sort |
Ibrahima Diouf |
title |
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
title_short |
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
title_full |
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
title_fullStr |
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
title_full_unstemmed |
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
title_sort |
cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2019-04-01 |
description |
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. |
topic |
Alzheimer's disease Iron Amyloid Biomarker Neurodegeneration Ferritin |
url |
http://www.sciencedirect.com/science/article/pii/S0969996118305369 |
work_keys_str_mv |
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