# Suppression of neuronal eEF2K alleviates cognitive deficits and apathy-like behavior in APP/PS1 AD model mice

## TL;DR

This study shows that reducing eEF2K activity in neurons improves cognitive issues and apathy in a mouse model of Alzheimer's disease.

## Contribution

The study reveals a novel therapeutic target, eEF2K, for treating cognitive and behavioral symptoms in Alzheimer's.

## Key findings

- Neuronal eEF2K inhibition improves cognitive deficits in APP/PS1 AD model mice.
- Reduced eEF2K activity alleviates apathy-like behavior and synaptic plasticity impairments.
- Targeting eEF2K signaling shows potential for treating dementia and NPS in AD and related dementias.

## Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by synaptic failure, cognitive impairment and neuropsychiatric symptoms (NPS). Apathy is the most common NPS seen in AD patients, and its underlying mechanisms remain unknown. Here, we investigated the roles of neuronal eukaryotic elongation factor 2 (eEF2) phosphorylation (by its kinase eEF2K) in AD-associated cognitive deficits and NPS. We performed a series of experiments using a multidisciplinary approach including genetics, behavioral assays, synaptic electrophysiology, and unbiased proteomics. The results demonstrated that neuron-specific inhibition of eEF2K and eEF2 phosphorylation can alleviate cognitive deficits, synaptic plasticity impairments, and apathy-like behavior in aged APP/PS1 AD model mice. Our findings indicate the therapeutic potential of targeting the eEF2K signaling in the treatment of dementia and NPS in AD and related dementias (ADRDs).