Journal
FRONTIERS IN NEUROLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2022.961842
Keywords
ferritin; sTrem2; iron; Alzheimer's Disease; neuroinflammation
Categories
Funding
- Alzheimer's Disease Neuroimaging Initiative (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
- Araclon Biotech
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- AbbVie
- Cogstate
- BioClinica, Inc.
- Elan Pharmaceuticals, Inc.
- Eisai Inc.
- Eli Lilly and Company
- GE Healthcare
- EuroImmun
- IXICO Ltd.
- F. Hoffmann-La Roche Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Fujirebio
- Lumosity
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lundbeck
- Merck Co., Inc.
- Neurotrack Technologies
- Meso Scale Diagnostics LLC.
- Servier
- NeuroRx Research
- Transition Therapeutics
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Laboratory for Neuro Imaging at the University of Southern California
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This study investigated the association between CSF ferritin and sTrem2, finding a significant correlation between them in the AD continuum, suggesting CSF ferritin as a potential biomarker for Trem2-indicated microglia function.
Brain iron accumulation, which is indicated in the cerebrospinal fluid (CSF) ferritin, is associated with the development of Alzheimer's Disease (AD). Studies have indicated that iron deposition might participate in Alzheimer's pathology through the induction of microglial activation. A soluble triggering receptor expressed on myeloid cells 2 (sTrem2) in CSF is increasingly recognized as a reliable indicator for microglia activity in the brain and participates in the development of neuroinflammation. However, the association between CSF ferritin and sTrem2 under the AD continuum has not been well-established. We enrolled individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were classified into healthy controls (HC, n = 46) and AD continuum (n = 105) in the combined strata of Amyloid/Tau/Neurodegeneration (ATN) mode and Clinical Dementia Rating (CDR) criteria. The associations between CSF ferritin (indicating iron burden) and sTrem2, as well as AD pathology, which is reflected by A beta 42, t-tau, and p-tau in CSF, were explored. CSF ferritin was significantly associated with sTrem2 among all participants (beta = 0.517, P < 0.001, FDR < 0.001), HC (beta = 0.749, P = 0.006, FDR = 0.010), and AD continuum (beta = 0.488, P < 0.001, FDR < 0.001), respectively. However, ferritin predicted the accelerated sTrem2 level in those with high ferritin (beta = 0.549, P = 0.036, FDR = 0.045). In conclusion, CSF ferritin serves as a potential biomarker of Trem2-indicated microglia function.
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