Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

Tsai, Yu‐Lin; Lü, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross‐Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

doi:10.1167/iovs.13-12888

Cited by 132 publications

(185 citation statements)

References 90 publications

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“…While the hallmark pathologies of AD have long been established in the brain, their manifestation in the human retina is a recent finding (11,26,(39)(40)(41)(42). We previously identified Aβ plaque pathology in postmortem retinas of definite AD patients as well as in early-stage cases (40).…”

Section: Introductionmentioning

confidence: 95%

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

et al. 2017

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BACKGROUND. Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. METHODS.Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. RESULTS.Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ 42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). CONCLUSION.The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.

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Section: Introductionmentioning

confidence: 95%

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

et al. 2017

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“…In addition, activated glial cells, hypertrophy of retinal pigmented epithelial cells, and choroidal inflammation have also been observed in the eyes of mouse models of Alzheimer's disease [3].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…It is the most common cause of dementia, affecting about 6 % of the population aged over 65, and the clinical incidence doubles every 5 years after 65 years of age [1,2]. Over 26 million people are estimated to suffer from AD, and this number is expected to quadruple by 2050 [3]. It is therefore a disease with a great social impact, leading to considerable impairment in quality of life for both patients, family members, and healthcare workers.…”

Section: Introduction-alzheimer's Disease (Ad)mentioning

confidence: 99%

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Cunha

Moura-Coelho

Proença

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on invivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.

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“…Nevertheless, all models showed retinal alterations even at various extents that sometimes preceded the cerebral lesions and in all models, the alterations are prevalent in the inner layer (4)(5)(6)(7)14). This is of importance considering the role of the visual disturbances in evaluating the learning and the memory (65).…”

Section: Discussionmentioning

confidence: 87%

“…In another AD model, the APP/PS1 mouse, hyper-expression of the phosphorylated tau was equally found in the retina, while there was little or no sign in the optic nerve, in the cornea, and in the lens (13). A marked thinning of the retinal choroid has been observed in the TgF344-AD rat model and in humans; in this model, visual acuity was lower than in age-matched rats (14). Antes et al (15) studied the effects of Apolipoprotein E4 (APO E4), the most prevalent genetic risk factor for the AD, in transgenic mice.…”

Section: Animal Modelsmentioning

confidence: 78%

Ocular and Visual Manifestation of the Alzheimer’s Disease: A Literature Review, Part I: Animal Models and Human Pathology

Raudino

2018

Arch Neurosci

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Context: The retina is a part of the Central Nervous System that is easy to study. The visual disturbances are frequent in Alzheimer's disease (AD) patients and sometimes, the AD begins with visual symptoms. This paper aims to review the existing literature on the involvement of the eye in the AD. In this first part, the animal models and the pathology in humans were examined. Evidence Acquisition: The Medline literature until March 2018 was surveyed. Results: Both animal models and pathological studies in humans demonstrate the impairment of the visual system in the AD, often in the early stages. Conclusions: A frequent and sometimes early involvement of the visual system was demonstrated but new studies are needed in order to investigate the degree of the visual impairment and in the animal models, the importance of the visual deficits in evaluating the cognitive deficits.

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Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

Cited by 132 publications

References 90 publications

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Ocular and Visual Manifestation of the Alzheimer’s Disease: A Literature Review, Part I: Animal Models and Human Pathology

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