Scholars

Rosemary Jackson, PhD

University of Dundee

Disease Area

Neuroscience

Focus

Validating a Method to Uncover and Progress Small Molecule Correctors of ApoE4

Scholar Profile

2024 ADDF-Harrington Scholar

The prevalence of Alzheimer’s disease (AD) in people over 65 years results from a complex web of biological processes. Focused on a “risk gene” that’s been implicated in late-onset AD, Dr. Jackson hopes to develop a therapy to delay cognitive decline and give people more good years.

As people age, Apolipoprotein E (ApoE), a lipid-transporting protein, plays increasingly significant roles in brain health. Dr. Jackson has been studying a specific gene variation—ApoE4. It’s considered the “risk gene” and has been shown to be the strongest genetic factor for developing AD. A large study of post-mortem brains has shown that an estimated 60% of late-onset AD patients are ApoE4 carriers.

“Another variation, ApoE3, differs from ApoE4 by a single amino acid, yet the structural difference causes changes in many biological pathways,” Dr. Jackson explains. “People who inherit two copies of ApoE4 are more likely to develop AD and be more susceptible to the consequences.”

With Harrington support, Dr. Jackson is screening small molecule compounds for a lead candidate that could act as an “ApoE corrector,” making ApoE4 function more like ApoE3. Potentially, her approach could replace current AD medications that cause side effects in ApoE4 individuals. “The challenge is getting a small molecule compound past the blood brain barrier,” Dr. Jackson says. “Once we do that, there’s hope for slowing AD at middle-age and improving quality of life in later years.”

"Adding ten good years to people's lives would make a big difference."