PILOT PROJECT--SYNAPSIN GENE EXPRESSION AS A BIOMARKER IN DEMENTIA

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The long term objective of this research approach is the development of an assay capable of assessing changes in the potential for plasticity that may occur in neurons in demential and aging. We have chosen the gene encoding the nerve terminal-specific protein synapsin as the experimental paradigm. The specific aim of the project is the investigation of changes in the expression of this gene encoding the nerve terminal-specific protein synapsin as the experimental paradigm. The specific aim of the project is the investigation of changes in the expression of this gene in dementia and during normal aging of the central nervous system. The hypothesis to be tested is whether assays of synapsin gene expressing can be used as sensitive indicators of changes in the developmental status, maturation and viability of neurons. The techniques to be employed for the assessment of synapsin gene expression in human and rat brain are: 1) RNA blot analysis of steady- state levels of synapsin mRNA; 2) nuclear run-off assay of changes in synapsin gene transcription; 3) correlation of temporal and spatial changes in synapsin mRNA levels by in situ hybridization histochemistry. The loss or impairment of synaptic connections in critical areas of the brain may produce important deficits, including those of memory, cognitive and behavioral function, associated with Alzheimer's Disease. The establishment of an assay capable of monitoring changes in neuronal plasticity may yield insight into the molecular basis of these changes.