Purpose: To investigate the relationship between MR image contrast associated with beta-amyloid (A) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with A plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues. Materials and Methods:With the aid of the previously developed histological coil, T* 2 -weighted images and R* 2 parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/ PS1 tissue slices. Results:The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T* 2 contrast of A-plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images. Conclusion:These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta-amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R* 2 relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in A plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with A plaques in humans and animals. THE FORMATION OF amyloid-beta (A) plaques is a neuropathological hallmark and a cardinal feature of Alzheimer's disease (AD). APP/PS1 transgenic mouse models that mimic the formation of human A plaques in the mouse brain are widely used as an animal model for AD investigations. The development of an imaging technology capable of visualizing and quantifying A plaques in animal models and in the AD brain is critically important for translational, preclinical and clinical research. The ability to delineate A plaques with MRI has been demonstrated ex vivo with human brain samples (1) and in vivo with the mouse model (2-4). Understanding the histological basis of MRI contrast associated with A plaques is essential in this endeavor. To achieve this goal, it is necessary to correlate MRI results with histological stains, which has been technologically challenging because of the limitations in co-registration of planar histology tissue samples with MR images. A prior study involving the innovation of a histological coil has addressed this long-standing difficulty (5). The ability to directly image histological samples is possible when using the developed histological radiofrequency (RF) coil design. Consequently, MR images and histology data from the same tissue sample can be directly overlaid and compared without uncertainties of co-registration between the two imaging modalities. The goal of the current study is to use this novel technology to (i) further optimize the m...
Alzheimer’s disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, twelve early stage AD patients and thirteen non-demented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The Blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and functional cognitive decline.
The dysregulation of iron metabolism in Alzheimer’s disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer’s disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer’s disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer’s disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer’s disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer’s pathology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.