Research ArticleAlzheimer’s Disease

Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer’s disease trigger BACE1 accumulation in axonal swellings

See allHide authors and affiliations

Science Translational Medicine  18 Nov 2020:
Vol. 12, Issue 570, eaba1871
DOI: 10.1126/scitranslmed.aba1871

Unraveling axonal traffic jam

The protease BACE1 participates in Aβ production and has been shown to accumulate in dystrophic neurons and contribute to axonal pathology in patients with Alzheimer’s disease (AD) and in animal models. The mechanisms mediating BACE1 accumulation are unclear. Here, Lomoio et al. showed that the Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) plays a main role in BACE1 localization. Deletion of Gga3 resulted in BACE1 accumulation and axonal swelling that was prevented by BACE inhibition. The authors identified a loss-of-function mutation in GGA3 in patients with AD, and Gga3 deletion worsened AD pathology in a mouse model. The results contribute to elucidate the mechanisms mediating axonal damage in AD.

View Full Text

Stay Connected to Science Translational Medicine