Related Experiment Video
Updated: Dec 21, 2025
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models
Christian Sacher1, Tanja Blume1,2, Leonie Beyer1
1Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University Munich, Munich, Germany.
Abstract:
Asymmetries of amyloid-β (Aβ) burden are well known in Alzheimer disease (AD) but did not receive attention in Aβ mouse models of Alzheimer disease. Therefore, we investigated Aβ asymmetries in Aβ mouse models examined by Aβ small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional Aβ PET scans of 5 different Aβ mouse models (APP/PS1, PS2APP, APP-SL70, App , and APPswe) together with 136 18-kDa translocator protein (TSPO) PET scans for microglial activation. The asymmetry index (AI) was calculated between tracer uptake in both hemispheres. AIs of Aβ PET were analyzed in correlation with TSPO PET AIs. Extrapolated required sample sizes were compared between analyses of single and combined hemispheres. Results: Relevant asymmetries of Aβ deposition were identified in at least 30% of all investigated mice. There was a significant correlation between AIs of Aβ PET and TSPO PET in 4 investigated Aβ mouse models (APP/PS1: R = 0.593, P = 0.001; PS2APP: R = 0.485, P = 0.019; APP-SL70: R = 0.410, P = 0.037; App : R = 0.385, P = 0.002). Asymmetry was associated with higher variance of tracer uptake in single hemispheres, leading to higher required sample sizes. Conclusion: Asymmetry of fibrillar plaque neuropathology occurs frequently in Aβ mouse models and acts as a potential confounder in experimental designs. Concomitant asymmetry of microglial activation indicates a neuroinflammatory component to hemispheric predominance of fibrillary amyloidosis.
Insights
Amyloid-beta (Aβ) plaque deposition shows significant asymmetry in Alzheimer
Area of Science:
- Neuroscience
- Alzheimer's Disease Research
- Animal Models
Background:
- Asymmetries in amyloid-beta (Aβ) burden are recognized in Alzheimer disease (AD) but understudied in AD mouse models.
- Investigating these asymmetries in mouse models is crucial for understanding AD pathology and experimental design.
- Microglial activation, a marker of neuroinflammation, is a key component of AD pathogenesis.
Purpose of the Study:
- To investigate Aβ deposition asymmetries in various Aβ mouse models using small-animal Positron Emission Tomography (PET).
- To determine if Aβ asymmetries correlate with microglial activation, assessed by 18-kDa translocator protein (TSPO) PET.
- To evaluate the impact of asymmetries on experimental sample size requirements.
Main Methods:
- Analysis of 523 cross-sectional Aβ PET scans from five Aβ mouse models (APP/PS1, PS2APP, APP-SL70, AppNL-G-F, and APPswe).
- Quantification of microglial activation using 136 TSPO PET scans.
- Calculation of asymmetry index (AI) for both Aβ and TSPO PET data between hemispheres and correlation analysis.
Main Results:
- Significant Aβ deposition asymmetries were observed in at least 30% of all mice studied.
- A strong correlation was found between Aβ PET AI and TSPO PET AI in four of the five Aβ mouse models.
- Hemispheric asymmetry increased tracer uptake variance, necessitating larger sample sizes for single-hemisphere analyses.
Conclusions:
- Fibrillar plaque neuropathology asymmetry is common in Aβ mouse models, potentially confounding experimental results.
- The correlation between Aβ and TSPO asymmetries suggests a neuroinflammatory contribution to amyloidosis hemispheric predominance.
- Understanding these asymmetries is vital for refining experimental designs and interpreting findings in AD mouse models.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
03:03Amyloid Fibrils