Year 3

Cholesterol metabolism in neurons is a key regulator in the development of two hallmark pathologies of Alzheimer’s disease; Aβ42 fragments, the main constituent of amyloid plaques and hyperphosphorylated Tau, the main constituent of neurofibrillary tangles (NFT). Our research has found that aberrant cholesterol mechanisms in familial AD hiPSC-derived neurons can profoundly affect generation of either toxic Aβ42 or pTau independently. Modulation of cholesterol biosynthesis, uptake and cellular trafficking in neurons represent  new and important clinical avenues to explore with future clinical trials using  novel or repurposed drugs.