# Quantitative 3D histochemistry reveals region-specific amyloid-β reduction by the antidiabetic drug netoglitazone

## TL;DR

This study shows that netoglitazone, a diabetes drug, reduces amyloid-beta plaques in specific brain regions of a mouse model for Alzheimer's disease.

## Contribution

The novel contribution is the use of quantitative 3D histology to identify region-specific drug effects on amyloid-beta plaques in Alzheimer's.

## Key findings

- Netoglitazone reduced the number and size of amyloid-beta plaques in specific brain regions.
- The drug improved cognition and reduced microglia activity in an Alzheimer's mouse model.
- Quantitative 3D histology provides a high-resolution view of drug efficacy across the whole brain.

## Abstract

A hallmark of Alzheimer’s disease (AD) is the extracellular aggregation of toxic amyloid-beta (Aβ) peptides in form of plaques. Here, we identify netoglitazone, an antidiabetic compound previously tested in humans, as an Aβ aggregation antagonist. Netoglitazone improved cognition and reduced microglia activity in a mouse model of AD. Using quantitative whole-brain three-dimensional histology (Q3D), we precisely identified brain regions where netoglitazone reduced the number and size of Aβ plaques. We demonstrate the utility of Q3D in preclinical drug evaluation for AD by providing a high-resolution brain-wide view of drug efficacy. Applying Q3D has the potential to improve pre-clinical drug evaluation by providing information that can help identify mechanisms leading to brain region-specific drug efficacy.