Inhalable Thioflavin S for the Detection of Amyloid Beta Deposits in the Retina

Barton, Shawn M; To, Eleanor; Rogers, Baxter P.; Whitmore, Clayton A.; Uppal, Manjosh; Matsubara, Joanne A.; Pham, Wellington

doi:10.3390/molecules26040835

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…The earlier presence of Aβ in the retina may be due to the pathology caused by the rd1 mutation. Interestingly, besides 5xFAD, we also noticed a few Aβ staining on WT retina, and this was also mentioned by Barton et al (2021) when they used inhalable thioflavin S (Barton et al, 2021). They also reported a significant association of Aβ deposits with RGCs.…”

Section: Discussionsupporting

confidence: 73%

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

et al. 2021

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One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

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Section: Discussionsupporting

confidence: 73%

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

et al. 2021

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“…Recent studies by Chibhabha et al (2020) ; Sidiqi et al (2020) , and Barton et al (2021) in the APP SWE /PS1 Δ E 9 transgenic mouse model further corroborated these findings via Aβ retinal curcumin imaging. In fact, numerous studies in AD rodent models have detected Aβ and its alloforms such as Aβ 40 and Aβ 42 in the AD retina ( Inestrosa et al, 2005 ; Dutescu et al, 2009 ; Liu et al, 2009 ; Alexandrov et al, 2011 ; Ardiles et al, 2012 ; Schon et al, 2012 ; Williams et al, 2013 ; Yang et al, 2013 ; Zhao et al, 2013 ; Park et al, 2014 ; Tsai et al, 2014 ; Du et al, 2015 ; Parthasarathy et al, 2015 ; Chiasseu et al, 2017 ; Grimaldi et al, 2018 ; Harrison et al, 2019 ).…”

Section: Introductionmentioning

confidence: 65%

Retinal Vasculopathy in Alzheimer’s Disease

et al. 2021

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The retina has been increasingly investigated as a site of Alzheimer’s disease (AD) manifestation for over a decade. Early reports documented degeneration of retinal ganglion cells and their axonal projections. Our group provided the first evidence of the key pathological hallmarks of AD, amyloid β-protein (Aβ) plaques including vascular Aβ deposits, in the retina of AD and mild cognitively impaired (MCI) patients. Subsequent studies validated these findings and further identified electroretinography and vision deficits, retinal (p)tau and inflammation, intracellular Aβ accumulation, and retinal ganglion cell-subtype degeneration surrounding Aβ plaques in these patients. Our data suggest that the brain and retina follow a similar trajectory during AD progression, probably due to their common embryonic origin and anatomical proximity. However, the retina is the only CNS organ feasible for direct, repeated, and non-invasive ophthalmic examination with ultra-high spatial resolution and sensitivity. Neurovascular unit integrity is key to maintaining normal CNS function and cerebral vascular abnormalities are increasingly recognized as early and pivotal factors driving cognitive impairment in AD. Likewise, retinal vascular abnormalities such as changes in vessel density and fractal dimensions, blood flow, foveal avascular zone, curvature tortuosity, and arteriole-to-venule ratio were described in AD patients including early-stage cases. A rapidly growing number of reports have suggested that cerebral and retinal vasculopathy are tightly associated with cognitive deficits in AD patients and animal models. Importantly, we recently identified early and progressive deficiency in retinal vascular platelet-derived growth factor receptor-β (PDGFRβ) expression and pericyte loss that were associated with retinal vascular amyloidosis and cerebral amyloid angiopathy in MCI and AD patients. Other studies utilizing optical coherence tomography (OCT), retinal amyloid-fluorescence imaging and retinal hyperspectral imaging have made significant progress in visualizing and quantifying AD pathology through the retina. With new advances in OCT angiography, OCT leakage, scanning laser microscopy, fluorescein angiography and adaptive optics imaging, future studies focusing on retinal vascular AD pathologies could transform non-invasive pre-clinical AD diagnosis and monitoring.

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“…The detection of β-amyloid deposits is also particularly important from the perspective of the diagnosis of neuroinflammation [ 156 ]. This is possible thanks to the use of immunohistochemical staining with thioflavin S [ 157 ]. Around them, microglial cells that are activated by inflammation accumulate and then join together, which, after detecting amyloid deposits, can also be visualized [ 158 ].…”

Section: Diagnostics Of the Inflammatory Process In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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Alzheimer’s disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer’s disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer’s disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

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Inhalable Thioflavin S for the Detection of Amyloid Beta Deposits in the Retina

Cited by 12 publications

References 43 publications

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

Retinal Vasculopathy in Alzheimer’s Disease

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

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