Quantitative image analysis of cerebral beta-amyloidosis in the APP(V717F) transgenic mouse model of Alzheimer's disease

Cindy Ellen Fishman, Purdue University

Abstract

Cerebral β-amyloidosis is a major feature of the neuropathology of Alzheimer's disease (AD). The APPV717F transgenic mouse is a model of cerebral β-amyloidosis used in the study of the pathogenesis and efficacy of potential treatments of AD. The histopathologic lesions of cerebral β-amyloidosis that occur in the APPV717F mouse can be measured quantitatively using image analysis. Image analysis methods that included novel sampling strategies at the microscopic slide and field levels were developed. These methods were used to study the effects of diet-induced hypercholesterolemia, an epidemiologic risk factor for AD, on the APP V717F mouse. Diet-induced hypercholesterolemia was associated with an increase in the severity of cerebral β-amyloidosis. However, variability (standard error) in the analyses was high. The model and analysis methods used were examined for sources of variability. The image analysis sampling methods were adequate to precisely represent the severity of the pathology in a given mouse and, within the limits of the analyses, were free from systematic errors that would introduce bias. The largest contribution to the standard error of the analyses was phenotypic variability inherent in the mouse model population. Measures of inter and intraanimal variability were used to perform power and variance component analyses for use in the design of future studies using the APPV717F mouse. Additionally, the data demonstrated that background genes of this outbred mouse strain influence phenotypic variability.

Degree

Ph.D.

Advisors

Thacker, Purdue University.

Subject Area

Pathology|Neurology|Statistics

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