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Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice
Maria F Falangola1, Sang-Pil Lee, Ralph A Nixon
1Center for Advanced Brain Imaging, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. falangola@nki.rfmh.org
Abstract:
This study confirms the presence of iron, co-localized with Abeta plaques, in PS/APP mouse brain, using Perls' stain for Fe3+ supplemented by 3,3'-diaminobenzidine (DAB) and Abeta immunohistochemistry in histological brains sections fixed with formalin or methacarn. In this study, the fixation process and the slice thickness did not interfere with the Perls' technique. The presence of iron in beta-amyloid plaques in PS/APP transgenic mice, a model of Alzheimer's disease (AD) pathology, may explain previous reports of reductions of transverse relaxation time (T2) in MRI studies and represent the source of the intrinsic Abeta plaque MR contrast in this model.
Insights
Iron is present in beta-amyloid plaques in a mouse model of Alzheimer's disease (AD). This finding may explain MRI signal changes observed in AD patients, linking iron accumulation to plaque visibility.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Alzheimer's disease (AD) is characterized by beta-amyloid (Abeta) plaques.
- Iron accumulation has been observed in AD brains, but its direct association with plaques is debated.
- Magnetic Resonance Imaging (MRI) studies show altered signal intensities in AD, potentially linked to plaque composition.
Purpose of the Study:
- To confirm the presence and location of iron within Abeta plaques in a transgenic mouse model of AD.
- To investigate the impact of histological fixation and sectioning on iron detection methods.
- To explore the role of iron in Abeta plaque-associated MRI contrast.
Main Methods:
- Utilized Perls' stain for Fe3+ detection.
- Combined with 3,3'-diaminobenzidine (DAB) and Abeta immunohistochemistry.
- Examined brain sections from PS/APP transgenic mice fixed with formalin or methacarn.
Main Results:
- Confirmed iron co-localization with Abeta plaques in PS/APP mouse brains.
- Demonstrated that fixation methods and slice thickness did not impede Perls' staining.
- Established iron as a component of beta-amyloid plaques in this AD model.
Conclusions:
- Iron is a constituent of beta-amyloid plaques in the PS/APP mouse model.
- This iron presence likely contributes to the reduced transverse relaxation time (T2) observed in MRI studies.
- Iron within plaques may be the source of intrinsic MR contrast for Abeta plaques in AD models.

