Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3307816

In Collections

This item can be found in the following collections:

Kenkhuis, B. (2022)

Iron-immune interactions in Alzheimer's disease

Doctoral Thesis
Alzheimer’s disease (AD) is the most common cause of dementia and quickly becoming one of the most burdening diseases of the century. Effective treatments are still missing, partially because its pathogenesis is still incompletely understood. This thesis explores the role of iron in AD, how it interacts with the immune system to influence disease pathogenesis and whether it could serve as potential biomarker. The first part of this thesis describes the importance of translational MRI, and how it can be used to increase our understanding of neurological diseases and help identify biomarkers. Subsequently, we used translational MRI to characterize the differences in iron accumulation in the brain between patients with AD and healthy elderly. The second part of this thesis investigated how the immune cells of the brain, microglia, interact with the accumulated iron. Using a combination of advanced multispectral immunofluorescence on brain tissue from AD patients and a human stem...Show moreAlzheimer’s disease (AD) is the most common cause of dementia and quickly becoming one of the most burdening diseases of the century. Effective treatments are still missing, partially because its pathogenesis is still incompletely understood. This thesis explores the role of iron in AD, how it interacts with the immune system to influence disease pathogenesis and whether it could serve as potential biomarker. The first part of this thesis describes the importance of translational MRI, and how it can be used to increase our understanding of neurological diseases and help identify biomarkers. Subsequently, we used translational MRI to characterize the differences in iron accumulation in the brain between patients with AD and healthy elderly. The second part of this thesis investigated how the immune cells of the brain, microglia, interact with the accumulated iron. Using a combination of advanced multispectral immunofluorescence on brain tissue from AD patients and a human stem-cell derived microglia model, we studied the activation pattern of iron-accumulating microglia in human brains and emulated microglial iron accumulation in vitro. This enabled us to study the effect of iron on the gene expression patterns and function of the brain’s immune cells.
Show less
Alzheimer's disease
MRI
Biomarker
Iron
Microglia
Neuroimmunology
Induced pluripotent stem cells
All authors
Kenkhuis, B.
Supervisor
Roon-Mom, W.M.C. van; Maarel, S.M. van der
Co-supervisor
Weerd, L. van der
Committee
Maagdenberg, A.M.J.M. van den; Vries, H.E. de; Eggen, B.J.L.; Ayton, S.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2022-06-08
ISBN (print)
9789464582369

Funding

Sponsorship
LUMC - Board of directors; Alzheimer Nederland; Alzheimer's Society UK; Eurolife