期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 88, 期 3, 页码 1115-1125出版社
IOS PRESS
DOI: 10.3233/JAD-220002
关键词
Alzheimer's disease; cerebrospinal fluid; ferritin; neurodegeneration; neuroinflammation
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- BristolMyers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. HoffmannLa Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Science and Technology Project of Huizhou [2017C0416032]
- Project of Young Innovative Talents in Colleges and Universities in Guangdong Province [2017GkQ NCX078]
- Science and Technology Project of Guangdong Province [2019B030316001]
- Guangzhou Municipal Key Discipline in Medicine [20212023]
This study investigated the associations of iron accumulation with neurodegenerative and inflammatory changes in Alzheimer's disease. The results showed that CSF ferritin levels were related to cognitive performance and other biomarkers, and higher levels were observed in more advanced stages of the disease.
Background: Increasing evidence has suggested that iron accumulation plays an important role in the onset and development of Alzheimer's disease (AD). However, the potential mechanism remains unclear. Objective: The present study investigated the associations of cerebrospinal fluid (CSF) ferritin, an indicator for brain iron load, with neurodegenerative and inflammatory changes in AD. Methods: The study involved 302 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). They were classified as normal controls (A-T-N-, n = 48), AD continuum (A+TN-, n = 46; A+TN+, n = 166), and suspected non-AD pathology (A-TN+, n = 42), according to the amyloid/tau/neurodegeneration (ATN) system. Group comparisons of CSF ferritin among groups were performed using one-way ANOVA. Linear regression models were used to test the relationships between CSF ferritin and cognitive assessments, and the associations between CSF ferritin and other biomarkers, respectively. Results: We found that CSF ferritin showed significant differences among the ATN groups, with higher concentration in more advanced categories (A+TN+). Furthermore, CSF ferritin level was independently related to cognitive performance (MMSE, ADAS-Cog13, and ADNI-mem). Linear regression analysis indicated positive relationships between CSF ferritin and phosphorylated tau and total tau, rather than A beta(42). Significant associations were revealed between CSF ferritin and inflammatory proteins, including TNF-alpha, TNFR1, TNFR2, ICAM1, VCAM1, TGF-beta 1, IL-9, and IP-10, respectively. Conclusion: Our results provide new insight into iron dysfunction in AD pathology and highlight elevated brain iron as a possible mechanism of neurodegeneration and neuroinflammation along AD continuum.
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