期刊
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
卷 89, 期 5, 页码 456-460出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jnnp-2017-316551
关键词
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资金
- ADNI (National Institutes of Health Grant) [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
- Biogen Idec
- Bristol-Myers Squibb Company
- Eisai
- Elan Pharmaceuticals
- Eli Lilly and Company
- F Hoffmann-La Roche and its affiliated company Genentech
- Innogenetics, NV
- IXICO
- Janssen Alzheimer Immunotherapy Research Development
- Johnson & Johnson Pharmaceutical Research Development
- Medpace
- Merck Co
- Meso Scale Diagnostics
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer
- Piramal Imaging
- Servier
- Synarc
- 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) programme is an Australian Government Initiative)
- Victorian Government
- GE Healthcare
Objective To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF beta-amyloid (A beta) and tau. Methods Mixed-effects models of CSF A beta(1-42) and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and A beta(1-42) for up to 5 years. Results In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (> 6.2 ng/mL) was associated with accelerated depreciation of CSF A beta(1-42) (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or A beta(1-42) in subjects with low baseline pathology. In simulation modelling of the natural history of A beta deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF A beta from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF A beta over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical A beta levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. Conclusions Iron might facilitate A beta deposition in Alzheimer's and accelerate the disease process.
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