Quantitative 3D histochemistry reveals region-specific amyloid-β reduction by the antidiabetic drug netoglitazone
Year: 2025
Type: article
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.
Authors: Catto, Francesca, Kirschenbaum, Daniel, Economides, Athena E., Reuss, Anna Maria, Trevisan, Chiara, Caredio, Davide, Dadgar-Kiani, Ehsan, Delic, Mirzet, Frick, Lukas, Weber-Stadlbauer, Ulrike, Litvinov, Sergey, Koumoutsakos, Petros, Lee, Jin Hyung, Aguzzi, Adriano
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6947699488
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