The magnetic brain: Alzheimer’s disease seen through iron

Samenvatting

Abnormal accumulation of iron is found in the brains of patients with different types of neurodegenerative diseases (NDs), especially Alzheimer’s disease (AD). Despite iron’s central role in the pathophysiology of NDs, the mechanisms of its toxicity are still not well understood. The lack of knowledge of the role of specific iron forms (SIFs) is a strongly limiting factor in the study of NDs. In my postdoctoral work I developed a methodology based on a novel combination of magnetic resonance and magnetometry, which can quantify different SIFs in brain tissue, including: (i) iron ions bound to complexes of low molecular weight, (ii) crystalline iron bound inside the main iron storage protein (ferritin) and (iii) iron-oxide mineral forms, without a protein shell, i.e. magnetite. Additionally, my method offers the possibility to relate these quantitative direct measurements of SIFs in post-mortem brain tissue to in vivo magnetic resonance imaging (MRI), which is commonly-used as an indirect method to ‘visualize’ brain iron. The first objective of my project will be to quantify the SIFs which accumulate in AD: this represents the most complete characterization of brain iron to be performed to-date. Second, I will characterize the magnetic properties of iron forms isolated from brain tissue and correlate them with cytotoxic effects, such as oxidative stress, neuronal cell death and changes in iron-regulatory proteins. This research will contribute to the fundamental understanding of the iron chemistry involved in the disease, and potentially to the future design of drugs to scavenge the toxic SIFs. Finally, knowledge of the molecular magnetic properties of SIFs will enable the optimization of MRI pulse sequences to measure SIFs in vivo. This proposal will add new knowledge to the basic pathophysiology of iron accumulation, and it also aims to translate this knowledge into more quantitative measurements in vivo, using MRI.

Kenmerken

Projectnummer

016.Veni.188.040

Hoofdaanvrager

Dr. L. Bossoni

Verbonden aan

Universiteit Leiden, Faculteit der Wiskunde en Natuurwetenschappen, Leids Instituut voor Onderzoek in de Natuurkunde (LION)

Uitvoerders

Dr. L. Bossoni

Looptijd

01/11/2017 tot 31/08/2020