%0 Conference Paper
%A Buettner, Felix
%A Reinert, Tilo
%A Jaeger, Carsten
%A Brammerloh, Malte
%A Morawski, Markus
%A Lipp, Ilona
%A Falkenberg, Gerald
%A Brueckner, Dennis Bjoern
%A Bazin, Pierre-Louis
%A Crockford, Catherine
%A Wittig, Roman
%A Weiskopf, Nikolaus
%A Kirilina, Evgeniya
%A Buettner, Felix
%T Lifespan Iron Accumulation inDopaminergic Neurons Studied byQuantitative MRI and X-ray Fluorescence
%M PUBDB-2024-06285
%D 2023
%X Dopaminergic neurons (DN) in the substantia nigra (SN) suffer from iron overload in age, increasing the risk for Parkinson’s disease (PD). Neuromelanin (NM) chelates iron, protecting DN against oxidative stress, but becomes toxic when oversaturated in age. Therefore, monitoring iron in DN is crucial for early PD diagnosis and understanding its pathophysiology. Herein, we studied iron accumulation in chimpanzee brains across the lifespan. We measured cellular iron in DN and extended the recently proposed non-invasive MRI-based method for DN-iron quantification to entire primate lifespan.22 postmortem brains of chimpanzees (0.1-56 y, 8 f) were ethically collected within the Evolution of Brain Connectivity (EBC) project. Quantitative maps of iron-sensitive effective transverse relaxation rate (R2*) were acquired on a 7T MRI scanner (Siemens Healthineers, Erlangen) using multiparametric mapping.For five brains (0.1,1.7,16,30 and 44 y), cellular iron quantification was performed using X-ray fluorescence microscopy (XRF) at the Deutsches Elektronen-Synchrotron (DESY). The biophysical model of iron-induced MRI contrast based on the static dephasing theory was informed by the cellular iron concentrations and used to estimate the contribution of DN to the effective transverse MRI relaxation rate (R2*) in the SN at different ages.The R2* in the SN and cellular iron load of DN both increased with age. The R2* in SN in adult chimpanzee brains (mean = 65.7 1/s, age >20 y) was similar to those in humans (69.2 1/s), qualifying the chimpanzee as a suitable animal model to study the lifespan iron accumulation.The cellular NM-iron accumulation determined with XRF in a large group of neurons (>200 per case) was well described by an exponential saturation with a time constant of 47(8) years. The averaged tissue iron concentration in SN, estimated using averaged R2* values, increased with a time constant of 27(16) years. This was substantially faster than NM-iron, indicating different underlying physiological processes for cellular accumulation in DN and total tissue iron levels.We linked the cellular iron concentration to the qMRI parameter R2* using our biophysical model and tested the model validity. The model was applicable for animals older than 16 years.We quantified the age-related iron accumulation of NM-clusters in DN in the SN of our closest relatives, chimpanzees, using XRF and demonstrated that its time constant differs from that of the overall tissue. We demonstrated that the biophysical model of iron-induced R2* in the SN is applicable after puberty opening the way for a non-invasive biomarker of DN density and iron load, which may be used to diagnose and monitor PD in humans.We quantified the lifespan accumulation of neuromelanin-bound iron in primate dopaminergic neurons using quantitative MRI and XRF for the first time.Our data helps to understand the role of iron in Parkinson and to develop an early-stage neuroimaging biomarker for dopaminergic neurodegeneration.
%B European Molecular Imaging Meeting
%C 12 Mar 2024 - 15 Mar 2024, Porto (Portugal)
Y2 12 Mar 2024 - 15 Mar 2024
M2 Porto, Portugal
%F PUB:(DE-HGF)6
%9 Conference Presentation
%U https://bib-pubdb1.desy.de/record/615824