Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model
Open accessAbstract
Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain presents an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n=8) and in suspected early stage cases (n=5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n=5). In APP(SWE)/PS1(∆E9) transgenic mice (AD-Tg; n=18) but not in non-Tg wt mice (n=10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n=4 mice per group). In live AD-Tg mice (n=24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n=11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies.
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In APPswe/PS1ΔE9 transgenic mice, Aβ plaques appear in retina at presymptomatic stages as early as 2.5 months, preceding detection in brain.
“In APPswe / PS1ΔE9 transgenic mice, Aβ plaques appeared in the retina of young transgenic AD mice at presymptomatic stages, as early as 2.5 months, preceding their detection in the brain.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Koronyo-Hamaoui et al., 2011
Systemic administration of curcumin to AD mice resulted in specific in vivo labeling of retinal Aβ plaques.
“In relation to this last point, it has been demonstrated that the systemic administration of curcumin to AD mice resulted in specific in vivo labeling of retinal Aβ plaques.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Koronyo-Hamaoui et al., 2011
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“…on machine learning, deep learning, threshold methods or their combination using microscopic images [2], PET images [41], or optical images [42], [43], [44] etc. Yoon, et al. [2] proposed segmentation based method to detect A β plaques using microscopic images for deep learning training to find…”
- Authors
- Koronyo-Hamaoui, M., Koronyo, Y., Ljubimov, A. V., Miller, C. A., Ko, M. K., Black, K. L., Schwartz, M., & Farkas, D. L.
- Affiliations
- Cedars-Sinai Medical Center (US)
- University of Southern California (US)
- Weizmann Institute of Science (IL)
- Corresponding author
- Farkas, Daniel L.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 54
- Pages
- S204-S217
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2991559
- OpenAlex
- W2047202120
- Cited by
- 672
- References
- 50
- Citations by year
- 2026: 38 · 2025: 56 · 2024: 47 · 2023: 45 · 2022: 54 · 2021: 71 · 2020: 76 · 2019: 53 · 2018: 51 · 2017: 39 · 2016: 39 · 2015: 27 · 2014: 22 · 2013: 22 · 2012: 23
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cedars-Sinai Medical Center
- National Institute on Aging (P50-AG05142, P50AG005142)
- National Eye Institute (R01 EY13431, R01EY013431)
- National Center for Research Resources (M01RR000425, M01-RR00425)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- Alzheimer's disease, amyloid plaques, retinal imaging, curcumin, APP/PS1 mice, non-invasive optical imaging, early diagnosis, immunotherapy, disease progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Curcumin, Disease Models, Animal, Coloring Agents, Female, Humans, Immunohistochemistry, Male, Mice, Transgenic, Microscopy, Fluorescence, Middle Aged, Retina, Spectrometry, Fluorescence, Imaging, Three-Dimensional, Mice, Plaque, Amyloid
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