Abstract

Neurodegenerative diseases (NDs) mercilessly transform a healthy adult brain into a progressively dysfunctional state. Differences in clinical manifestations (cognitive dysfunction in Alzheimer’s disease versus motor dysfunction in Parkinson’s disease) are the result of damage to specific brain cell types in specific brain regions. Effective therapies for NDs are currently very limited, partly due to the fact that most therapeutic discovery screens have relied on limited types of cultured cells that incompletely mimic the relevant disease state in the brain. In recent years we have employed and refined techniques that enable the identification of affected cell types and disease mechanisms in complex tissues. Although our work focuses on mouse models of brain diseases (prion diseases for example) the approaches we employ could also be adapted to other species and tissues.