<i>Gga3</i> deletion and a <i>GGA3</i> rare variant associated with late onset Alzheimer’s disease trigger BACE1 accumulation in axonal swellings
Selene Lomoio, Rachel Willen, WonHee Kim, Kevin Ho, Edward K. Robinson, Dmitry Prokopenko, Matthew Kennedy, Rudolph E. Tanzi, Giuseppina Tesco
Abstract
deletion exacerbates axonal dystrophies in a mouse model of AD before β-amyloid (Aβ) deposition. Our study strongly supports a role for GGA3 in AD pathogenesis, where GGA3 loss of function triggers BACE1 axonal accumulation independently of extracellular Aβ, and initiates a cascade of events leading to the axonal damage distinctive of the early stage of AD.
Topics & Concepts
DiseaseChemistryMedicineCancer researchInternal medicineAlzheimer's disease research and treatmentsEpigenetics and DNA MethylationGenomics and Rare Diseases