The effect of iron in MRI and transverse relaxation of amyloid-beta plaques in Alzheimer's disease

Dysregulation of neural iron is known to occur during the progression of Alzheimer's disease. The visualization of amyloid-beta (A) plaques with MRI has largely been credited to rapid proton relaxation in the vicinity of plaques as a result of focal iron deposition. The goal of this work was to determine the relationship between local relaxation and related focal iron content associated with A plaques. Alzheimer's disease (n=5) and control tissue (n=3) sample slices from the entorhinal cortex were treated overnight with the iron chelator deferoxamine or saline, and microscopic gradient-echo MRI datasets were taken. Subsequent to imaging, the same slices were stained for A and iron, and then compared with regard to parametric R-2* relaxation maps and gradient-echo-weighted MR images. A plaques in both chelated and unchelated tissue generated MR hypo-intensities and showed relaxation rates significantly greater than the surrounding tissue. The transverse relaxation rate associated with amyloid plaques was determined not to be solely a result of iron load, as much of the relaxation associated with A plaques remained following iron chelation. The data indicate a dual relaxation mechanism associated with A plaques, such that iron and plaque composition synergistically produce transverse relaxation.Copyright (c) 2014 John Wiley & Sons, Ltd.