# Targeting Adipocyte Enhancer-Binding Protein 1 to Induce Microglial Phenotype Shift for Immunotherapy in Alzheimer’s Disease

## TL;DR

This study explores how targeting AEBP1 in microglia can shift their activity to reduce inflammation and neuronal damage in Alzheimer’s disease.

## Contribution

The study is the first to show that AEBP1 can modulate microglial inflammation and may serve as a target for Alzheimer’s immunotherapy.

## Key findings

- Downregulation of AEBP1 in activated microglia reduces immune response via the NFκB pathway.
- AEBP1 expression is elevated in Alzheimer’s disease mouse brains.
- Targeting AEBP1 reduces amyloid beta accumulation and microglial inflammation.

## Abstract

Neuroinflammation, a key contributor to neurodegenerative diseases, results from excessive microglial activation. Microglia that respond to pathogenic molecules switch to the M1 type and secrete various immune cytokines, which can cause neuronal damage. Therefore, our study focused on molecules that can enhance the neuroprotective role of microglia and reduce neuronal damage. The adipocyte enhancer-binding protein 1 (AEBP1) gene is known for its role in regulating immune responses in macrophages. However, its role in neuroinflammation has not been fully explored. Therefore, we investigated the role of AEBP1 in microglial cells activated by lipopolysaccharide (LPS). First, we confirmed that AEBP1 is expressed in LPS-activated microglia and demonstrated that downregulation of AEBP1 using shRNA in activated microglia reduced the immune response via the nuclear factor-kappa-B (NFκB) pathway. These results promote a shift toward neuroprotective M2 microglia, thereby reducing neuronal damage. Next, we confirmed that the expression of AEBP1 was elevated in the brains of Alzheimer’s disease (AD) mice. Additionally, animal experiments to assess the therapeutic effects of AEBP1 showed that microglia gathered around amyloid beta (Aβ) and reduced its size. Taken together, our results provide the first evidence that AEBP1 can reduce inflammatory activity in microglia, suggesting its potential as a target molecule for immunotherapy.