UCL President and Provost Michael Spence meets Professor Sir John Hardy, whose groundbreaking genetics research at UCL has revolutionised treatment for Alzheimer's. John always dreamed of working at UCL Queen Square Institute of Neurology, the world's leading neurological research centre. But he was rejected for his current position in 1992 and had to wait 15 years before finally getting the job in 2007.

Working with Alzheimer's families, he discovered mutations in the gene for the amyloid protein, and in an influential paper proposed that the build-up of the amyloid protein in the brain is where Alzheimer's begins – a theory that's now the basis for new treatments.

Remarkably, 30 years later, we still don't know what amyloid does in healthy brains. We just know that when it deposits in the hippocampus, it kills neurons and destroys the ability to form new memories.

Two new drugs based directly on John’s research – lecanemab and donanemab – are ‘monoclonal antibodies’ that work by clearing amyloid build-ups in the brain, slowing disease progression. The next frontier? Anti-tau therapies, already under development at Queen Square. Like diabetes, Alzheimer's will likely require multiple treatments.

John's had four major "hits" when it comes to finding key genes involved in the development of neurological conditions: amyloid, tau, alpha-synuclein (Parkinson's), and TREM2. "There's nothing like the thrill of finding a gene," he says. When asked about retirement? "No, I want one more gene!"

Credits:

Presenter: Dr Michael Spence, UCL President & Provost

Guest: Professor Sir John Hardy, from the UCL Queen Square Institute of Neurology

Produced by UCL Communications and UCL Educational Media