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Updated: Aug 20, 2026
Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
Published on: July 26, 2011
Part of membrane-bound Abeta exists in rafts within senile plaques in Tg2576 mouse brain
Hideko Kokubo1, Takaomi C Saido, Nobuhisa Iwata
1Gunma University School of Health Sciences, 3-39-15 Showa-machi, 371-8514 Maebashi, Japan.
Abstract:
To clarify whether rafts are the site of abnormal amyloid beta protein (Abeta) deposition, we examined the ultrastructural localization of both flotillin-1 (pre-embedding) and Abeta (post-embedding) in Tg2576 mouse brains. After observing the exact areas of senile plaques by reflection contrast microscopy, we observed these same plaques under an electron microscope. Membrane-bound Abeta was predominantly observed on plasma membranes of small processes in diffuse plaques. Non-fibrillar and fibrillar Abeta was increased in primitive plaques, and the fibrillar form was predominant in mature plaques. The number of flotillin-1-positive rafts per field in mature plaques was prominently less than those outside of the plaques, in diffuse plaques and in primitive plaques. The colocalization of flotillin-1 with Abeta42 appeared approximately 10% of flotillin-1-positive rafts within senile plaques, while there was no colocalization found outside of the plaques. This study ultrastructurally demonstrated that part of membrane-bound Abeta exists in lipid rafts within senile plaques, and suggests that rafts could be one of the sites for initial Abeta deposition.
Insights
Lipid rafts may be an initial site for amyloid beta protein (Abeta) deposition in the brain. This study found Abeta within rafts in senile plaques, suggesting their role in early Alzheimer's disease pathology.
Area of Science:
- Neuroscience
- Cell Biology
- Alzheimer's Disease Research
Background:
- Amyloid beta protein (Abeta) deposition is a hallmark of Alzheimer's disease.
- The precise location of initial Abeta accumulation within brain cells remains unclear.
Purpose of the Study:
- To investigate if lipid rafts are involved in the abnormal deposition of amyloid beta protein (Abeta).
- To determine the ultrastructural localization of Abeta and flotillin-1 within senile plaques in a mouse model.
Main Methods:
- Utilized Tg2576 mouse brains for analysis.
- Employed reflection contrast microscopy to identify senile plaques.
- Performed pre-embedding immunolabeling for flotillin-1 and post-embedding immunolabeling for Abeta, followed by electron microscopy.
Main Results:
- Membrane-bound Abeta was observed on plasma membranes in diffuse plaques.
- Increased non-fibrillar and fibrillar Abeta was found in primitive and mature plaques, respectively.
- Flotillin-1-positive rafts were less abundant in mature plaques, with approximately 10% colocalization with Abeta42 within senile plaques.
Conclusions:
- Ultrastructural evidence indicates that membrane-bound Abeta is present within lipid rafts in senile plaques.
- Lipid rafts are suggested as a potential site for the initial deposition of Abeta, contributing to Alzheimer's disease pathogenesis.
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