Apoer2-ICD Translatome

ApoE4, the most significant genetic risk factor for late-onset Alzheimers disease (AD), sequesters a pro-synaptogenic receptor, Apoer2, which protects against amyloid-beta toxicity. Apoer2 plays a critical role in synaptic function, which is regulated by alternative splicing of the receptor. Moreover, Apoer2 processing releases an intracellular domain (ICD) capable of regulating transcription and its splicing can ameliorate behavioral deficits in an AD mouse model. However, the role of this splicing in transcriptional regulation is unknown. Here, we assessed in vivo changes in ribosome-associated hippocampal transcripts after lentiviral delivery of Apoer2-ICD splice variants in wild-type, conditional knockout, and cleavage-resistant Apoer2 mice by RNA-sequencing.