Dataset Information

In vivo Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

ABSTRACT: Alzheimer's disease (AD) is characterized by amyloid beta (A?) plaques in the brain detectable by highly invasive in vivo brain imaging or in post-mortem tissues. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate tissue to assess A? load in AD. Using curcumin, a FluoroProbe that binds to A?, we labeled and measured the retinal fluorescence in vivo and compared with the immunohistochemical measurements of the brain and retinal A? load in the APP/PS1 mouse model. In vivo retinal images were acquired every 2 months using custom fluorescence scanning laser ophthalmoscopy (fSLO) after tail vein injections of curcumin in individual mice followed longitudinally from ages 5 to 19 months. At the same time points, 1-2 mice from the same cohort were sacrificed and immunohistochemistry was performed on their brain and retinal tissues. Results demonstrated cortical and retinal A? immunoreactivity were significantly greater in Tg than WT groups. Age-related increase in retinal A? immunoreactivity was greater in Tg than WT groups. Retinal A? immunoreactivity was present in the inner retinal layers and consisted of small speck-like extracellular deposits and intracellular labeling in the cytoplasm of a subset of retinal ganglion cells. In vivo retinal fluorescence with curcumin injection was significantly greater in older mice (11-19 months) than younger mice (5-9 months) in both Tg and WT groups. In vivo retinal fluorescence with curcumin injection was significantly greater in Tg than WT in older mice (ages 11-19 months). Finally, and most importantly, the correlation between in vivo retinal fluorescence with curcumin injection and A? immunoreactivity in the cortex was stronger in Tg compared to WT groups. Our data reveal that retina and brain of APP/PS1 Tg mice increasingly express A? with age. In vivo retinal fluorescence with curcumin correlated strongly with cortical A? immunohistochemistry in Tg mice. These findings suggest that using in vivo fSLO imaging of AD-susceptible retina may be a useful, non-invasive method of detecting A? in the retina as a surrogate indicator of A? load in the brain.

SUBMITTER: Sidiqi A

PROVIDER: S-EPMC7350785 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>In vivo</i> Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

Sidiqi Ahmad A Wahl Daniel D Lee Sieun S Ma Da D To Elliott E Cui Jing J To Eleanor E Beg Mirza Faisal MF Sarunic Marinko M Matsubara Joanne A JA

Frontiers in neuroscience 20200703

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques in the brain detectable by highly invasive <i>in vivo</i> brain imaging or in post-mortem tissues. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate tissue to assess Aβ load in AD. Using curcumin, a FluoroProbe that binds to Aβ, we labeled and measured the retinal fluore ...[more]

PMID: 32719582

Similar Datasets

Project description:UnlabelledAlzheimer disease (AD) is a fatal neurodegenerative disorder characterized by progressive neuronal loss and cognitive decline. The lack of reliable and objective diagnostic markers for AD hampers early disease detection and treatment. Growing evidence supports the existence of a dysregulation in brain copper trafficking in AD. The aim of this study was to investigate brain copper trafficking in a transgenic mouse model of AD by PET imaging with (64)Cu, to determine its potential as a diagnostic biomarker of the disorder.MethodsBrain copper trafficking was evaluated in 6- to 8-mo-old TASTPM transgenic mice and age-matched wild-type controls using the (64)Cu bis(thiosemicarbazone) complex (64)Cu-GTSM (glyoxalbis(N(4)-methyl-3-thiosemicarbazonato) copper(II)), which crosses the blood-brain barrier and releases (64)Cu bioreductively into cells. Animals were intravenously injected with (64)Cu-GTSM and imaged at 0-30 min and 24-25 h after injection. The images were analyzed by atlas-based quantification and texture analysis. Regional distribution of (64)Cu in the brain 24 h after injection was also evaluated via ex vivo autoradiography and compared with amyloid-β plaque deposition in TASTPM mice.ResultsCompared with controls, in TASTPM mice PET image analysis demonstrated significantly increased (by a factor of ~1.3) brain concentration of (64)Cu at 30 min (P < 0.01) and 24 h (P < 0.05) after injection of the tracer and faster (by a factor of ~5) (64)Cu clearance from the brain (P < 0.01). Atlas-based quantification and texture analysis revealed significant differences in regional brain uptake of (64)Cu and PET image heterogeneity between the 2 groups of mice. Ex vivo autoradiography showed that regional brain distribution of (64)Cu at 24 h after injection did not correlate with amyloid-β plaque distribution in TASTPM mice.ConclusionThe trafficking of (64)Cu in the brain after administration of (64)Cu-GTSM is significantly altered by AD-like pathology in the TASTPM mouse model, suggesting that (64)Cu-GTSM PET imaging warrants clinical evaluation as a diagnostic tool for AD and possibly other neurodegenerative disorders.

Dataset Information

In vivo Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

Publications

<i>In vivo</i> Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets