REVIEW article
Front. Dement.
Sec. Translational Research in Dementia
Volume 4 - 2025 | doi: 10.3389/frdem.2025.1585124
This article is part of the Research TopicStudying Dementia in 3D: Basic Techniques and ApplicationsView all 3 articles
Three-dimensional organotypic mouse brain slices to study Alzheimer´s disease pathologies: a review
Provisionally accepted
- Innsbruck Medical University, Innsbruck, Austria
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Alzheimer´s disease (AD) is a severe neurodegenerative brain disorder molecularly characterized by extracellular (b-amyloid plaques, intraneuronal tau neurofibrillary tangles, cholinergic neuron death, neuroinflammation, vascular damage, and astroglial and microglial activation. AD is a complex disorder, and ˃ 99% of all cases are sporadic and occur around 65 years of age. Because of this complex disorder, in vitro experiments are limited; however, three-dimensional organotypic brain slices may offer the best alternative for studying the mechanisms of the AD process. This perspective/review provides an overview of how to study the general aspects of AD ex vivo and focuses on (a) b-amyloid plaques in brain slices, (b) tau pathology induced by chemical drugs, (c) cell death of cholinergic neurons and protection by nerve growth factor, (d) activation of astrocytes and microglia, and (e) vascular pathologies, including the role of platelets. Furthermore, we investigated (f) how microcontact printing on brain slices can be used to study the spreading of b-amyloid and tau, and (g) how brain slices can help identify novel human AD biomarkers.
Keywords: Alzheimers disease, organotypic 3D culture, brain slice, Pathology, review
Received: 28 Feb 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Humpel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Christian Humpel, Innsbruck Medical University, Innsbruck, Austria
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