Postmortem T2*- Weighted MRI Imaging of Cortical Iron Reflects Severity of Alzheimer’s Disease

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. T2*-weighted MRI was performed on postmortem cortical tissue of controls, late-onset AD (LOAD), and early-onset AD (EOAD) followed by histology and correlation analyses. Combining ex vivo high-resolution MRI and histopathology revealed that: 1) 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.

Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration

“…The copyright holder for this this version posted October 20, 2020. ; https://doi.org/10.1101/2020.10.15.20206102 doi: medRxiv preprint 5 described above, with the exception of the echo timing, which was increased as the iron concentration was much lower in these control cases: The first echo time was 12.5 ms long, and the inter-echo time was 10.7 ms (26).…”

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

“…AD is the most common neurodegenerative disease characterized by neurofibrillary tangles (NFTs) composed of Tau protein. Levels of iron and ferritin (iron storage protein) in brain tissue are associated with the amount of amyloid deposition (Bulk et al, 2018;Gong et al, 2019). Deletion of hippocampal neurons and astrocyte proliferation by inducing GPX4 deletion in adult mice, this change links AD to ferroptosis (Yoo et al, 2012).…”

Treating Alzheimer's disease by targeting iron

“…Iron levels in the brain accumulate with age (Aquino et al, 2009), which may engender risk of disease. In AD, cortical iron levels are elevated beyond the already high levels that occur during age, as measured by various methods in post-mortem tissue (Andrasi, Farkas, Scheibler, Reffy, & Bezur, 1995;Bulk et al, 2017;Bulk et al, 2018;Collingwood et al, 2005;Connor, Menzies, St Martin, & Mufson, 1992;De Reuck et al, 2014;Duce et al, 2010;Galazka-Friedman et al, 2011;Goodman, 1953;Hallgren & Sourander, 1960;Smith et al, 2010;Smith, Harris, Sayre, & Perry, 1997;van Duijn et al, 2017).…”

“…The amount of iron (Bulk et al, 2018) and ferritin (the major ironbinding protein of the cell; Kwiatek-Majkusiak et al, 2015) in brain tissue is associated with the extent of amyloid deposition. As well as being elevated in neuronal tissue, iron is enriched in the amyloid plaque itself (Meadowcroft, Peters, Dewal, Connor, & Yang, 2014), where the iron is observed to be found in a mineralized magnetite species in humans and mice models (Ayton, James, & Bush, 2017;Everett et al, 2018;Plascencia-Villa et al, 2016;Telling et al, 2017).…”