# Role of apoE-apoER2 interactions in CNS neurons

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $484,579

## Abstract

PROJECT SUMMARY
The ε4 allele of apolipoprotein E (apoE4) is the most important genetic risk factor for late-onset sporadic
Alzheimer's disease (LOAD). ApoE is a secreted glycoprotein that binds to a number of single-pass
transmembrane receptors of the low-density-lipoprotein receptor family, including apoER2 (official gene name
= LRP8). Interestingly, human apoER2 is subject to a high degree of alternative splicing events and notably
one of the top 10 of all neuronal genes related to exon-skipping splicing events. We have identified and
confirmed the expression of a large number of alternatively spliced apoER2 receptors in human brain, many of
which contain a different number of ligand binding domains which alter the binding of human apoE protein to
apoER2. However, the functional consequences of differential apoE-apoER2 interactions, downstream
receptor signaling and neuronal function for these naturally occurring human apoER2 splice variants remain
incompletely understood. The goal of this proposal is to define the functional consequences of specific apoE-
apoER2 interactions that could have major implications for our understanding of synaptic plasticity associated
with learning and memory and the role of apoE4 in LOAD.

## Key facts

- **NIH application ID:** 10213620
- **Project number:** 5R01AG059762-04
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Uwe Beffert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $484,579
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213620

## Citation

> US National Institutes of Health, RePORTER application 10213620, Role of apoE-apoER2 interactions in CNS neurons (5R01AG059762-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10213620. Licensed CC0.

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