Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-β Protein Precursor Transgenic Mice

Area of Science:

• Neuroscience
• Pathology
• Genetics

Background:

• Transgenic mouse models expressing amyloid-β protein precursor (AβPP) with Alzheimer's disease (AD)-linked mutations are crucial tools for studying Aβ amyloidosis.
• These models exhibit diverse Aβ generation and aggregation patterns, influencing brain function and disease pathogenesis.

Purpose of the Study:

• To quantitatively compare amyloid plaque burdens and plaque sizes across four distinct AβPP transgenic mouse lines.
• To directly compare plaque burdens in these mouse models with those observed in human Alzheimer's disease cases.

Main Methods:

• Quantitative analysis of dense-core amyloid plaques using Thioflavin S staining in the cortex and hippocampus of AβPP transgenic mice.
• Comparison of plaque burdens and size distributions across different ages and brain regions within mouse lines.
• Direct comparison of mouse plaque burdens to pathologically confirmed Alzheimer's disease cases from the Nun Study.

Main Results:

• Significant variation in plaque burdens among the four transgenic lines, differing by up to an order of magnitude.
• Plaque burdens in 5XFAD mice were substantially higher than in Tg2576 and rTg9191 mice at comparable ages.
• Plaque-size distributions varied depending on the mouse line and brain region, changing across the lifespan.
• Cortical plaque burdens in Tg2576, APPSwePS1ΔE9, and 5XFAD mice ultimately surpassed those found in human Alzheimer's disease cases.

Conclusions:

• AβPP transgenic mouse models exhibit considerable variability in amyloidosis, necessitating careful selection for Alzheimer's disease research.
• The quantitative data provides a valuable resource for understanding the relationship between Aβ toxicity in mice and human AD pathogenesis.
• Certain transgenic mouse lines demonstrate plaque burdens that exceed human AD pathology, highlighting their potential utility for studying advanced disease stages.