An important goal of AD research is to identify interventions that maintain brain function, potentially by inhibiting the formation or improving the clearance of neurotoxic aggregates, or by promoting resistance to, or recovery from, damage. A number of biological processes have been associated with AD, including cholesterol metabolism, inflammation, and response to misfolded proteins such as increased expression of heat shock proteins [20]. The link with lipid metabolism is supported for example by the essential role of APOE in lipid transport in the brain [13], [14]. However, these processes have not been unequivocally ordered into a pathogenic cascade, and the molecular mediators and correlates of each are largely unknown. Microarray gene expression profiling provides an opportunity to observe processes that are common for normal aging, AD, and other neurodegenerative diseases, as well as to detect the differences between these conditions and disentangle their relationships. We profiled over six hundred postmortem samples assembled in the Harvard Brain Tissue Resource Center (HBTRC, McLean Hospital, Belmont, MA). We used metagene (factor) analysis [21], [22], [23], [24], [25] to distinguish several major gene expression
