Comparing Alzheimer’s Mouse Models Through Quantitative Amyloid Plaque Mapping
Liu P, Reichl JH, Rao ER, McNellis BM, Huang ES, Hemmy LS, Forster CL, Kuskowski MA, Borchelt DR, Vassar R, Ashe KH, Zahs KR. Quantitative comparison of dense-core amyloid plaque accumulation in amyloid-β protein precursor transgenic mice. J Alzheimers Dis 2017;56(2):743-761. doi: 10.3233/JAD-161027.
Background: Alzheimer’s disease involves the accumulation of amyloid-β (Aβ) plaques, but transgenic mouse models expressing human Aβ precursor protein (AβPP) vary widely in plaque development and distribution. Comparing these models quantitatively can clarify how plaque pathology progresses and how well each model replicates human disease.
Hypothesis: This study hypothesized that distinct AβPP transgenic mouse lines would show significant differences in the timing, magnitude and regional distribution of dense-core amyloid plaque accumulation.
Methods: The authors examined four AβPP transgenic lines—5XFAD, APPSwePS1ΔE9, Tg2576 and rTg9191—using Thioflavin S staining to visualize dense-core plaques in cortex and hippocampus. Plaque burdens and areas were quantified stereologically with the Stereo Investigator system’s Area Fractionator and Nucleator modules. Additional imaging was performed with an Axio Imager microscope, an AxioCam digital camera and a Nikon TiE deconvolution microscope.
Results: Dense-core plaques appeared earliest and most abundantly in 5XFAD mice, followed by APPSwePS1ΔE9, Tg2576 and rTg9191. At 15 months, cortical plaque burden in 5XFAD mice was about 4.5 times higher than in 21-month-old Tg2576 and 15 times higher than in 24-month-old rTg9191. Plaque-size distributions changed with age and brain region. In three mouse lines, cortical plaque burdens eventually exceeded those measured in human Alzheimer’s cortex.
Conclusions: The study concludes that dense-core plaque accumulation differs by more than an order of magnitude among AβPP transgenic lines, reflecting genetic and biochemical variability. These quantitative differences highlight the need for careful model selection and standardized measurement methods when interpreting Aβ-related pathology in AD research.
