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Title: Profiling gene expression in Alzheimer's disease
Author: Brooks, W. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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Alzheimer’s disease is a debilitating neurodegenerative disease expected to increase in prevalence during the next few decades. Familial Alzheimer’s disease cases have revealed some molecules that appear to be involved in the disease pathogenesis. However, factors fully explaining the vast majority of case of Alzheimer’s disease which are sporadic, wait to be determined. The present study conducted a broad survey of gene expression in Alzheimer’s disease post mortem tissue with the aim of identifying gene expression products involved in this disease. Initially, a study was carried out to determine the effects of post mortem interval on gene expression assessment by cDNA array hybridisation. This study used mouse tissue in which the post mortem delay prior to freezing could be controlled. Observations from this study led to the conclusion that it is acceptable to assess gene expression in samples with varying PMIs. Samples derived from Alzheimer diseased and control human post mortem tissues were then compared to reveal differences in gene expression at the RNA level. The brain area under investigation was the hippocampus which is important for memory and is known to be affected in Alzheimer’s disease. Initially, five samples (2 Alzheimer’s disease, 3 controls) were screened against Affymetrix GeneChip HG-U133A arrays . The findings from this study were used, along with findings reported by other researchers, to identify candidates whose expression appeared to be altered in Alzheimer’s disease. Semi-quantitative Real-Time PCR was used to verify differential expression of the genes of interest in a greater number of samples (6 Alzheimer’s disease, 5 controls). This resulted in the identification of 13 statistically significant differentially expressed genes in Alzheimer’s disease from the 67 investigated. These included transcripts involved in ubiquitination, neurotransmission and energy metabolism amongst others. The biological significance of these findings is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available