4.5 Article

The Associations of Cerebrospinal Fluid Ferritin with Neurodegeneration and Neuroinflammation Along the Alzheimer's Disease Continuum

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

  1. Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
  2. National Institute on Aging
  3. National Institute of Biomedical Imaging and Bioengineering
  4. AbbVie
  5. Alzheimer's Association
  6. Alzheimer's Drug Discovery Foundation
  7. Araclon Biotech
  8. BioClinica, Inc.
  9. Biogen
  10. BristolMyers Squibb Company
  11. CereSpir, Inc.
  12. Cogstate
  13. Eisai Inc.
  14. Elan Pharmaceuticals, Inc.
  15. Eli Lilly and Company
  16. EuroImmun
  17. F. HoffmannLa Roche Ltd
  18. Genentech, Inc.
  19. Fujirebio
  20. GE Healthcare
  21. IXICO Ltd.
  22. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  23. Johnson & Johnson Pharmaceutical Research & Development LLC.
  24. Lumosity
  25. Lundbeck
  26. Merck Co., Inc.
  27. Meso Scale Diagnostics, LLC.
  28. NeuroRx Research
  29. Neurotrack Technologies
  30. Novartis Pharmaceuticals Corporation
  31. Pfizer Inc.
  32. Piramal Imaging
  33. Servier
  34. Takeda Pharmaceutical Company
  35. Transition Therapeutics
  36. Canadian Institutes of Health Research
  37. Science and Technology Project of Huizhou [2017C0416032]
  38. Project of Young Innovative Talents in Colleges and Universities in Guangdong Province [2017GkQ NCX078]
  39. Science and Technology Project of Guangdong Province [2019B030316001]
  40. Guangzhou Municipal Key Discipline in Medicine [20212023]

向作者/读者索取更多资源

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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