# NRN1 as a therapeutic target for Alzheimer's disease

## TL;DR

This study explores NRN1 as a potential therapeutic target for Alzheimer's disease, showing its link to cognitive resilience and changes in expression during disease progression.

## Contribution

The study identifies NRN1 as a novel therapeutic candidate for Alzheimer's disease using multi-omics and experimental validation.

## Key findings

- NRN1 expression in excitatory neurons decreases with increasing donor pseudo-progression in Alzheimer's disease.
- The Abcam ab64186 antibody detects NRN1 protein, suggesting it forms a homodimer in vitro and in vivo.
- NRN1 protein levels are similar in controls and tauopathy cases, as well as in Tau P301S and non-transgenic mice.

## Abstract

Neuritin‐1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory‐Sage‐SGC‐JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT‐AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA‐AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

NRN1 has a TREAT‐AD target risk score of 3.29 out of 5. Based on single‐nucleus RNA sequencing from SEA‐AD, NRN1 expression in excitatory neurons tends to decrease with increasing donor pseudo‐progression. Abcam ab64186 polyclonal NRN1 antibody detects NRN1 protein in vitro and in vivo at molecular weights that suggest NRN1 forms a homodimer. NRN1 protein abundance is comparable among controls and primary tauopathy cases, as well as Tau P301S mice and non‐transgenic littermates at 3 and 9 months.

These findings advance the investigation of NRN1 as a therapeutic candidate for AD.

NRN1 is associated with cognitive resilience to AD.Based on snRNA‐seq from SEA‐AD, NRN1 expression in excitatory neurons tends to decrease with increasing donor pseudo‐progression.Abcam ab64186 polyclonal NRN1 antibody detects NRN1 protein in vitro and in vivo at molecular weights that suggest NRN1 forms a homodimer.NRN1 protein abundance is comparable among controls and primary tauopathy cases, as well as Tau P301S mice and non‐transgenic littermates at 3 and 9 months.

NRN1 is associated with cognitive resilience to AD.

Based on snRNA‐seq from SEA‐AD, NRN1 expression in excitatory neurons tends to decrease with increasing donor pseudo‐progression.

Abcam ab64186 polyclonal NRN1 antibody detects NRN1 protein in vitro and in vivo at molecular weights that suggest NRN1 forms a homodimer.

NRN1 protein abundance is comparable among controls and primary tauopathy cases, as well as Tau P301S mice and non‐transgenic littermates at 3 and 9 months.