The earliest clinical manifestation of Alzheimer's disease (AD) is cognitive impairment caused by synaptic dysfunction. ApoE4, the primary risk factor for late-onset AD, disrupts synaptic homeostasis by impairing synaptic ApoE receptor trafficking. Alternative splicing of ApoE receptor-2 (Apoer2) maintains synaptic homeostasis. In this issue, Hinrich et al () show that Apoer2 splicing is impaired in human AD brains and murine AD models and that restoring normal splicing in the mouse rescues amyloid-induced cognitive defects.
ASJC Scopus subject areas
- Molecular Medicine