In Vivo Characterization of a Loss-of-Function GGA3 Rare Variant Associated with Alzheimer’s Disease

2020, 2022

We have identified a novel genetic mutation in a gene called GGA3. This mutation increases the risk of developing Alzheimer’s disease. GGA3 is essential for the transport of BACE1, a key enzyme in AD, in neurons. We discovered that the absence of GGA3 is toxic for neurons. More importantly, this AD-linked GGA3 mutation produces a toxic effect similar to the one observed when GGA3 is completely absent in neurons. Our data indicate this new genetic mutation makes neurons sick because GGA3 has lost its ability to transport BACE1. These findings are important for the development of personalized therapies for subjects carrying this specific mutation.

Funding to Date



Studies of Novel AD Genes, Translational


Giuseppina Tesco, M.D., Ph.D.