Tau Isoform Regulation in Neurodegenerative Diseases

Dementia affects more than 20 million people worldwide and more than 4 million people in the United States. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two of the most common forms of dementia. Toxic, insoluble aggregates of tau protein, called neurofibrillary tangles (NFTs) are pathological signatures in AD and FTD. The amount of tau accumulation correlates with disease severity, but its role in the initiation of the disease is unknown. The objective of Dr. D’Souza’s research is to understand the mechanism for tau gene expression during normal development, normal aging, and disease development in cell cultures and mouse neuronal systems. Mice bred to express the human tau genomic construct will be a powerful system to study tau gene expression during brain development and aging, and could help identify new candidates for therapeutic interventions.