# Alternative Splicing of ApoER2 in Alzheimer's Disease

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $18,850

## Abstract

PROJECT SUMMARY: Age and the ɛ4 allele of apolipoprotein E (apoE) are the two greatest risk factors for
developing Late Onset Alzheimer’s Disease (LOAD). As there is no known cure for or cause of LOAD,
understanding the mechanism underlying known risk factors is paramount for moving therapeutic research
forward. ApoE mediates its physiological effects in the brain by binding to cognate receptors like apoER2, which
is found in multiple splice isoforms or variants that are precisely regulated. Recent studies have discovered a
novel link between aging, neurodegeneration and alternative splicing. Interestingly, alternative splicing of the
apoE receptor apoER2 is altered in Alzheimer’s disease (AD). Therefore, abnormal alternative splicing in aging
and neurodegeneration may alter the interactome of the key AD risk factor APOE through apoER2, influencing
APOE physiological function and highlighting a new scientific paradigm through which to investigate the role of
APOE in LOAD. The overall goal of this proposal is to investigate whether splicing of apoER2 is altered
in AD and to uncover modifiers of apoER2 splicing events. The central hypothesis is that apoER2 isoform
balance is perturbed in AD due to altered posttranslational regulation of splicing factors, correlating with
pathology development across the brain. To investigate this hypothesis, two specific aims are proposed. In Aim
1, the isoform distribution of apoER2 will be determined across AD Braak stage and brain region compared to
healthy individuals using single molecule long read sequencing and qPCR. In Aim 2, regulation of a specific
apoER2 splicing event by a splicing factor will be probed using a variety of in vitro techniques including RNA-
Immunoprecipitations, splicing reporter assays and gel shift assays. Completion of this proposal will be highly
significant, providing a novel scientific model through which to view conferred APOE risk in AD: altered
splicing regulation of the cognate receptor apoER2. This proposal incorporates bioinformatics, synaptic
biology and RNA biology into one integrated training plan providing the applicant a well-rounded and rich
fellowship training experience. This is accomplished by an expansive network of supporting sponsors and
collaborators who have pledged to guide the applicant through the proposed research and facilitate her
development into an independent research neuroscientist.

## Key facts

- **NIH application ID:** 10396990
- **Project number:** 5F31AG069498-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Christina Marie Gallo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $18,850
- **Award type:** 5
- **Project period:** 2021-04-07 → 2022-04-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396990

## Citation

> US National Institutes of Health, RePORTER application 10396990, Alternative Splicing of ApoER2 in Alzheimer's Disease (5F31AG069498-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10396990. Licensed CC0.

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