Journal
NEUROBIOLOGY OF DISEASE
Volume 124, Issue -, Pages 335-339Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2018.12.010
Keywords
Alzheimer's disease; Iron; Amyloid; Biomarker; Neurodegeneration; Ferritin; Fluorodeoxyglucose
Categories
Funding
- ADNI (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- GE Healthcare
- Innogenetics, N. V.
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Australian Research Council
- Australian National Health & Medical Research Council (NHMRC)
- CRC for Mental Health (the Cooperative Research Centre (CRC) program is an Australian Government Initiative)
- Victorian Government
- Operational Infrastructure Support Grant
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beta-Amyloid pathology is elevated in similar to 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 beta-amyloid pathology determined by established cut-off values in CSF t-tau/A beta(42) ratio. Nineteen cognitively normal participants with low t-tau/A beta(42), and 71 participants with high t-tau/A beta(42) 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/A beta(42) participants (beta[SE] = -0.066 [0.017]; P = .0002), but not in people with low t-tau/A beta(42) (-0.029 [0.049]; P = .554). These data implicate iron as a contributing factor to neurodegeneration associated with beta-amyloid pathology, and highlight CSF ferritin as a complementary prognostic biomarker to the t-tau/A beta(42) ratio that predicts near-term risk for disease progression.
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