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.
Source: PLoS ONE
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: National Science Foundation, Michael J. Fox Foundation for Parkinson's Research, Human Frontier Science Program, Fondazione Gelu, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Zürich, NOMIS Stiftung, National Institutes of Health, Horizon 2020 Framework Programme, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering
Awards: Modifiers and cofactors of prion replication, toxicity and tropism, G2490659655, Mapping gut-to-brain transmission of prion protein, Innovating high-resolution novel imaging approaches to elucidate mechanisms of prion-like spreadingof neurodegenerative disease, The prion protein in health and disease, PrP and its receptor GPR126: guardians of axomyelinic integrity and druggable targets against demyelinating diseases, G6400767305, G7983326833, G8858395165, G9000317295
OpenAlex ID: W4410112217