Marjolein Bulk

Cortical Iron Reflects Severity of Alzheimer’s Disease

Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer’s disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl’s histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex.

Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease

Previous MRI studies reported cortical iron accumulation in early-onset (EOAD) compared to late-onset (LOAD) Alzheimer disease patients. However, the pattern and origin of iron accumulation is poorly understood. This study investigated the histopathological correlates of MRI contrast in both EOAD and LOAD. T2*-weighted MRI was performed on postmortem frontal cortex of controls, EOAD, and LOAD. Images were ordinally scored using predefined criteria followed by histology. Nonlinear histology-MRI registration was used to calculate pixel-wise spatial correlations based on the signal intensity. EOAD and LOAD were distinguishable based on 7T MRI from controls and from each other. Histology-MRI correlation analysis of the pixel intensities showed that the MRI contrast is best explained by increased iron accumulation and changes in cortical myelin, whereas amyloid and tau showed less spatial correspondence with T2*-weighted MRI. Neuropathologically, subtypes of Alzheimers disease showed different patterns of iron accumulation and cortical myelin changes independent of amyloid and tau that may be detected by high-field susceptibility-based MRI.

Quantitative comparison of different iron forms in the temporal cortex of Alzheimer patients and control subjects

We present a quantitative study of different molecular iron forms found in the temporal cortex of Alzheimer (AD) patients. Applying the methodology we developed in our previous work, we quantify the concentrations of non-heme Fe(III) by Electron Paramagnetic Resonance (EPR), magnetite/maghemite and ferrihydrite by SQUID magnetometry, together with the MRI transverse relaxation rate

COARSE PLAQUES ARE MORE COMMON IN EARLY ONSET COMPARED TO LATE ONSET ALZHEIMER’S DISEASE

({{\rm{R}}}_{2}^{\ast })

Cerebral Amyloid Angiopathy With Vascular Iron Accumulation and Calcification: A High-Resolution Magnetic Resonance Imaging Histopathology Study

(R2⁎), to obtain a systematic view of molecular iron in the temporal cortex. Significantly higher values of

MAPPING OF NATRIURETIC PEPTIDES AND THEIR RECEPTORS IN THE BRAINS OF NON-DEMENTED HUMAN SUBJECTS AND PATIENTS WITH ALZHEIMER’S DISEASE

{{\rm{R}}}_{2}^{\ast }