Abstract
Adequate assessment of plaque deposition levels in the brain of mouse models of Alzheimer disease (AD) is required in many core issues of studies on AD, including studies on the mechanisms underlying plaque pathogenesis, identification of cellular factors modifying plaque pathology, and developments of anti-AD drugs. The present study was undertaken to quantitatively evaluate plaque deposition patterns in the brains of the two popular AD models, Tg2576 and Tg-APPswe/PS1dE9 mice. Coronally-cut brain sections of Tg2576 and Tg-APPswe/PS1dE9 mice were prepared and plaque depositions were visualized by staining with anti-amyloid β peptides antibody. Microscopic images of plaque depositions in the prefrontal cortex, parietal cortex, piriform cortex and hippocampus were obtained and the number of plaques in each region was determined by a computer-aided image analysis method. A series of optical images representing a gradual increase of plaque deposition levels were selected in the four different brain regions and were assigned in each with a numerical grade of 1-6, where +1 was lowest and +6, highest, so that plaques per unit in mm2 increased "sigmoidally" over the grading scales. Analyzing plaque depositions using the photographic plaque reference panels and a computer-aid image analysis method, it was demonstrated that the brains of Tg2576 mice started to accumulate predominantly small plaques, while the brains of Tg-APPswe/PS1dE9 mice deposited relatively large plaques.
Highlights
Transgenic Tg2576 mice of Alzheimer disease (AD) express human APP695 with double mutations (K670N-M671L), which results in amyloid plaque depositions in the brain starting from 9 months of age (Hsiao et al, 1996; Benzing et al, 1999; Kawarabayashi et al, 2001)
Using the 6-grade photographic plaque reference and a computer program-aid image analysis method, we demonstrated that the brains of Tg2576 mice started to accumulate predominantly small plaques, while the brains of Tg-amyloid precursor protein (APP)/presenilin 1 (PS1) mice deposited relatively large plaques
Tg-APP/PS1 mice were introduced more recently (Jankowsky et al, 2001), this AD model gains another popularity because this model is available and amyloid plaque deposition starts as early as 6.5 months of age (Jankowsky et al, 2001, 2003)
Summary
Transgenic Tg2576 mice of AD express human APP695 with double mutations (K670N-M671L), which results in amyloid plaque depositions in the brain starting from 9 months of age (Hsiao et al, 1996; Benzing et al, 1999; Kawarabayashi et al, 2001). Tg-APPswe/PS1dE9 (Tg-APP/PS1 for short) mice represent another animal model of AD that expresses mutant forms of human APP and presenilin 1, which result in amyloid plaque deposition in the brain starting from. The levels of plaque deposition in the brains are evaluated by measuring the number of plaques, plaque sizes, or total area covered by plaques, usually by using a computer-aid image analysis program (Lim et al, 2000; Bacher et al, 2008; Ho et al, 2008). Some easy methods are needed to complement the limited features of computer-aid image analysis methods or a simple manual counting method, provided that unbiased, quantitative and quantitative features are hold
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