Three-Dimensional Study of Alzheimer’s Disease Hallmarks Using the iDISCO Clearing Method
Open accessAbstract
Amyloidosis is a major problem in over one hundred diseases, including Alzheimer's disease (AD). Using the iDISCO visualization method involving targeted molecular labeling, tissue clearing, and light-sheet microscopy, we studied plaque formation in the intact AD mouse brain at up to 27 months of age. We visualized amyloid plaques in 3D together with tau, microglia, and vasculature. Volume imaging coupled to automated detection and mapping enables precise and fast quantification of plaques within the entire intact mouse brain. The present methodology is also applicable to analysis of frozen human brain samples without specialized preservation. Remarkably, amyloid plaques in human brain tissues showed greater 3D complexity and surprisingly large three-dimensional amyloid patterns, or TAPs. The ability to visualize amyloid in 3D, especially in the context of their micro-environment, and the discovery of large TAPs may have important scientific and medical implications.
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Astrocytic expression of APOE3 and APOE3Ch reduced plaque burden and yielded more compact plaques, with APOE3Ch showing the stronger effect.
“We observed that astrocytic expression of APOE3 and APOE3Ch reduced plaque burden and yielded more compact plaques, as assessed by plaque sphericity [14, 15] and mean X-34 intensity, with APOE3Ch showing the stronger effect.”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [14]
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RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“…origin and the role of these hallmarks, including the debate about the importance of oligomers versus amyloid plaques and NFTs (Berger et al., 2007; Lesne et al., 2006 ;Walsh et al., 2002), but we believe that a better understanding of the threedimensionality of disease hallmarks and their complex…”
BackgroundRetractedSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
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Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes
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- Authors
- Liebmann, T., Renier, N., Bettayeb, K., Greengard, P., Tessier-Lavigne, M., & Flajolet, M.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Flajolet, Marc
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 16
- Issue
- 4
- Pages
- 1138-1152
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5040352
- OpenAlex
- W2465504877
- Cited by
- 218
- References
- 6
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 30 · 2023: 15 · 2022: 25 · 2021: 39 · 2020: 29 · 2019: 18 · 2018: 18 · 2017: 11 · 2016: 1
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Fisher Center for Alzheimer's Research Foundation
- Fondation pour la Recherche sur Alzheimer
- National Institute on Aging (R01AG047781, P01AG009464)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- Alzheimer's disease, amyloid plaques, iDISCO, tissue clearing, light-sheet microscopy, 3D imaging, tau protein, microglia, vascular system, plaque quantification, human brain tissue, mouse brain
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Brain, Disease Models, Animal, Humans, Mice, Inbred C57BL, Amyloid beta-Peptides, Microglia, Imaging, Three-Dimensional, Mice, Plaque, Amyloid
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