# Effect of APP copy number variants in Alzheimer's disease and and Down Syndrome on Reelin expression and function

> **NIH NIH R43** · REELIN THERAPEUTICS, INC. · 2023 · $259,999

## Abstract

Abstract
Chronic inflammatory pathology represents a major source of damage to the brain observed in
Down’s syndrome (DS). Although the precise etiology of these diseases is often unknown,
excessive leukocyte extravasation is a substantial contributor to the tissue damage/inflammation
and our recent data show a prominent role of the plasma protein, Reelin in this process.
Furthermore, we have now shown that it is possible, using anti-Reelin monoclonal antibodies, to
deplete the plasma of Reelin, which results in a significant reduction of a wide range of vascular
adhesion molecule expression. Thus, in contrast to the current methods of depleting individual
adhesion molecules or immune receptors, our anti-Reelin approach systematically
downregulates all major inflammation-driven adhesion proteins on the vascular endothelium.
The purpose of this proposal is to demonstrate the role of Reelin in DS by 1) validating the
therapeutic potential of mitigating chronic inflammatory milieu with an anti-Reelin antibody in an
DS mouse model and 2) identifying high affinity Reelin antibodies for future therapeutic
development.

## Key facts

- **NIH application ID:** 10760161
- **Project number:** 1R43AG084450-01
- **Recipient organization:** REELIN THERAPEUTICS, INC.
- **Principal Investigator:** Laurent Calvier
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $259,999
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760161

## Citation

> US National Institutes of Health, RePORTER application 10760161, Effect of APP copy number variants in Alzheimer's disease and and Down Syndrome on Reelin expression and function (1R43AG084450-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10760161. Licensed CC0.

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