NRN1 as a therapeutic target for Alzheimer's disease.

Abstract

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD). METHODS: 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. RESULTS: 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. DISCUSSION: These findings advance the investigation of NRN1 as a therapeutic candidate for AD.