Statistical aspects of quantitative image analysis of beta-amyloid in the APP(V717F) transgenic mouse model of Alzheimer's disease

Cerebral beta -amyloidosis is a central part of the neuropathology of Alzhe imer's disease (AD). Quantitation of beta -amyloid plaques in the human AD brain, and in animal models of AD, is an important study endpoint in AD res earch. Methodologic approaches to the measurement of beta -amyloid in the b rain vary between investigators, and these differences affect outcome measu res. Here, one quantitative approach to the measurement of beta -amyloid pl aques in brain sections was analyzed for sources of variability due to samp ling. Brain tissue was from homozygous APP(V717F) transgenic male mice. Sam pling variables were at the mouse and microscopic slide and field levels. R esults indicated that phenotypic variability in the mouse sample population was the largest contributor to the standard error of the analyses. Within each mouse, variability between slides or between fields within slides had smaller effects on the error of the analyses. Therefore, when designing stu dies of adequate power, in this and in other similar models of cerebral bet a -amyloidosis, sufficient numbers of mice per group must be included in or der for change in mean plaque burden attributable to an experimental variab le to outweigh phenotypic variability. (C) 2001 Elsevier Science B.V. All r ights reserved.