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Post-mortem T2*- weighted MRI imaging of cortical iron reflects severity of Alzheimer’s Disease

Marjolein Bulk, Boyd Kenkhuis, Linda M. van der Graaf, Jelle J. Goeman, Remco Natté, Louise van der Weerd
doi: https://doi.org/10.1101/279513
Marjolein Bulk
aDepartment of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
bDepartment of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
cPercuros BV, Leiden, The Netherlands
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  • For correspondence: m.bulk@lumc.nl
Boyd Kenkhuis
aDepartment of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
bDepartment of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
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Linda M. van der Graaf
bDepartment of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
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Jelle J. Goeman
dDepartment of Statistics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
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Remco Natté
eDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
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Louise van der Weerd
aDepartment of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
bDepartment of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
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Abstract

The value of iron-based MRI changes for the diagnosis and staging of Alzheimer’s disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study determined the cortical distribution pattern of MRI contrast changes in cortical regions selected based on the known distribution pattern of tau pathology and investigated whether MRI contrast changes reflect the underlying AD pathology in the different lobes.Embedded Image-weighted MRI was performed on post-mortem cortical tissue of controls, late-onset AD, and early-onset AD followed by histology and correlation analyses. Combining ex-vivo high-resolution MRI and histopathology revealed that: LOAD and EOAD have a different distribution pattern of AD pathological hallmarks and MRI contrast changes over the cortex, with EOAD showing more severe MRI changes; (2) per lobe, severity of AD pathological hallmarks correlates with iron accumulation, and hence with MRI. Therefore, iron-sensitive MRI sequences allow detection of the cortical distribution pattern of AD pathology ex-vivo.

AD
Alzheimer’s disease
EOAD
early-onset AD
GM
gray matter
IRP
iron regulating proteins
LOAD
late-onset AD
MCI
mild cognitive impairment
PBS
phosphate buffered saline
QSM
quantitative susceptibility mapping
WM
white matter
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 10, 2018.
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Post-mortem T2*- weighted MRI imaging of cortical iron reflects severity of Alzheimer’s Disease
Marjolein Bulk, Boyd Kenkhuis, Linda M. van der Graaf, Jelle J. Goeman, Remco Natté, Louise van der Weerd
bioRxiv 279513; doi: https://doi.org/10.1101/279513
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Post-mortem T2*- weighted MRI imaging of cortical iron reflects severity of Alzheimer’s Disease
Marjolein Bulk, Boyd Kenkhuis, Linda M. van der Graaf, Jelle J. Goeman, Remco Natté, Louise van der Weerd
bioRxiv 279513; doi: https://doi.org/10.1101/279513

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