From cDNA microarrays to high-throughput proteomics. Implications in the search for preventive initiatives to slow the clinical progression of Alzheimer's disease dementia

Alzheimer's disease (AD) is the most common form of dementia, affecting as many as four million elderly people. It results from abnormal changes in th e brain that most likely begin long before cognitive impairment and other c linical symptoms become apparent. Little is known about the changes precedi ng or accompanying initiation of the disease. Using cDNA microarray, we pre viously reported candidate gene products whose expression is altered in the cerebral cortex of cases at risk for AD dementia. However, it is possible that the cDNA microarray evidence might have underestimated post-transcript ional modifications, and as a result, provided only a partial view of the b iological problem of interest. Based on this hypothesis, we initiated a ser ies of parallel high-throughput proteomic studies. We found that, consisten t with the. cDNA microarray evidence, the expression of proteins involved i n synaptic activities was also altered in the brains of early AD cases. The se studies support the feasibility and usefulness of high-throughput cDNA a nd protein microarray techniques to examine the sequential changes of disti nctive gene expression patterns in the brain as a function of the progressi on of AD dementia. Our preliminary results also support the utility of high -throughput proteomic methodologies as a means to identify novel AD biomark ers from cerebral spinal fluid and/or from serum.