Technical Report Number
Understanding the pathogenesis in the early stages of late-onset Alzheimer's disease (LOAD) can help in gaining important mechanistic insights into this devastating neurodegenerative disorder. Alzheimer's disease (AD) is characterised by extensive cell death with disease progression. In this paper laser capture microdissection (LCM) based gene expression profiling, which is able to profile gene expression in a single cell type, is employed to analyse the gene expression regulation of incipient AD. Our analysis shows that LCM based gene expression profiling of neurons has a critical advantage over the conventional gene expression profiling method which uses samples of mixed cell types and does not account for cell loss. A natural question that arises in this situation is how can we say that a gene is "down-regulated" when it just may not be present due to the absence of cells? Our investigation on expression regulation also resulted in 1633 significant genes, from which we identified 15 DNA repair genes that had elevated or lowered levels of mRNA expression. Many key players involved in the defense against DNA damage were present in this list, and many genes were involved in the base-excision repair pathway. Our results indicate that the base excision repair pathway, a predominant pathway in neurons, fails to handle the DNA damage in an efficient manner and is a compelling explanation for many of the pathological features of LOAD.
Ray, Monika and Zhang, Weixiong, "Single cell expression profiling reveals major disruption of DNA repair capacity in incipient Alzheimer's Disease" Report Number: WUCSE-2007-36 (2007). All Computer Science and Engineering Research.