ArticleInvestigative ophthalmology & visual science2025
Three-Dimensional β-Amyloid Burden Correlation Between the Eye and Brain in Alzheimer's Disease Mice Using Light-Sheet Fluorescence Microscopy.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Exploring Alzheimer Disease from a Retinal and Ocular Perspective.Biomedicines · 2026Review
- Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.Frontiers in synaptic neuroscience · 2026Review
- "Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size."bioRxiv : the preprint server for biology · 2025Article
- The role of astrocytes in ischemic stroke - mechanisms, functions and treatment.Frontiers in cell and developmental biology · 2025Review
- Longitudinal assessment of intraocular pressure in the 5xFAD mouse model of Alzheimer's disease.Frontiers in neurologyArticle
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8 authors.
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Abstract
Purpose: Recent studies have highlighted the significance of peripheral β-amyloid (Aβ) deposition, identifying the eye as a potential early detection site for Alzheimer's disease (AD). However, previous two-dimensional AD ocular studies have been unable to establish a clear correlation between the three-dimensional Aβ accumulation in the entire eyeball and brain while preserving structural integrity. This study employed a combined brain amyloid positron emission tomography/magnetic resonance (PET/MR) and light-sheet fluorescence microscopy (LSFM) platform to assess whether the three-dimensionally measured Aβ burden in the eyeball correlates with that in the brain. Methods: Thirteen eyeballs (6 AD, 7 control) and 17 brains (10 AD, 7 control) were collected from ten 44-week-old 5xFAD and seven control mice. The samples underwent tissue clearing and staining with thioflavin S (Aβ), anti-CD11b (microglia), and anti-ACSA-2 (astrocytes) for LSFM imaging and quantified via 3D surface volume. Standardized uptake value ratios from [18F]Flutemetamol PET/MR were also calculated. Results: AD eyeballs presented significantly greater plaque-like surface volumes (median, 51,091,002 µm³ [interquartile range, 38,488,272-64,869,828]) than controls (229,293 µm³ [115,863-311,5320]; P = 0.001). AD brains exhibited higher [18F]Flutemetamol uptake and greater plaque-like surface volumes (898,634,368 µm³ [556,263,488-1,105,326,720]) than controls (33,320,178 µm³ [26,842,538-62,716,956]; P < 0.001). A strong positive correlation was observed between the plaque-like surface volumes in the brain and that in the eyeball (r = 0.810, P = 0.001). No significant correlations were found in other morphologic parameters. Conclusions: Our observation of a strong correlation between the three-dimensional Aβ burden in the whole eyeball and brain advances our understanding of the systemic nature of Aβ pathology and suggests ocular Aβ as a potential independent predictor of brain Aβ burden.
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