[DOWNLOAD] "Modifiers of Beta-Amyloid Metabolism and Deposition in Mouse Models of Alzheimer's Disease" by Stefanie Schrump ~ Book PDF Kindle ePub Free
eBook details
- Title: Modifiers of Beta-Amyloid Metabolism and Deposition in Mouse Models of Alzheimer's Disease
- Author : Stefanie Schrump
- Release Date : January 19, 2013
- Genre: Medical,Books,Professional & Technical,
- Pages : * pages
- Size : 22055 KB
Description
Alzheimer’s disease (AD) is a progressive form of dementia that is definitively diagnosed postmortem by the presence of beta-amyloid (Aβ) deposition. Aβ is the proteolytic processing product of the amyloid precursor protein (APP). While genetic evidence supports APP as disease causative in some cases of AD, it accounts for only 1% of the predicted 79% heritability of the disease. The majority of genetic factors involved in AD are largely unknown, as is how they interact with the environmental factors responsible for the disease. Although genetic screens in humans have been unsuccessful in reproducibly identifying genetic and environmental risk factors for AD, the congenic R1.40 mouse model provides a reliable method to identify genetic risk factors for disease. The present study examines the effect of genetic background on Aβ levels throughout life. The C57BL/6J strain has high levels of Aβ early in life, corresponding to Aβ deposition at 13 months of age. In contrast, the DBA/2J and 129S1/SvImJ strains have reduced levels of Aβ early in life, with delayed deposition until 24 months of age. Finally, the A/J strain has Aβ levels significantly higher than those in the C57BL/6J strain but never deposits. Unique genetic mapping resources available for these strains, including chromosome substitution strains (A/J) and congenic lines (DBA/2J) were used to identify specific loci responsible for alterations in Aβ metabolism. The regions containing genetic modifiers of Aβ deposition were narrowed to chromosome 11 in the A/J strain, chromosome 1 in the DBA/2J strain and have identified a gene (C5) responsible for reduced Aβ deposition on chromosome 2 in the DBA2/J strain. This thesis also examines the complex interaction between genes and environment, showing that genetic background can affect susceptibility to postulated environmental modifiers of Alzheimer’s disease. Hemizygous R1.40 animals on three genetic backgrounds, DBA/2J, C57BL/6J and 129S1/SvImJ were fed high-fat/high-cholesterol (HF/HC) or low-fat/low-cholesterol (LF/LC) diets for 8 weeks. Despite all strains being exposed to a HF/HC diet, only the C57BL/6J strain had alterations in Aβ levels, which appeared to be due to diet-induced strain-specific differential gene expression.