Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer’s Transgenic Mice

Liu, Bingqian; Rasool, Suhail; Yang, Zhikuan; Glabe, Charles G.; Schreiber, Sidney S.; Ge, Jian; Tan, Zhiqun

doi:10.2353/ajpath.2009.090159

Cited by 159 publications

(201 citation statements)

References 70 publications

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“…If Aβ changes in the retina are to be useful for AD screening, significant differences from the changes observed in retinal diseases must be identified. Aβ plaques as well as retinal microvascular deposition of Aβ have been identified in the retinas of AD transgenic mouse models [133]. If such changes occur in human AD, they could possibly be detected by non-invasive optical scattering [110], Raman spectroscopic or fluorescent tagging techniques.…”

Section: (Figure 7)mentioning

confidence: 99%

“…Plaques and tangles have not been found in the human retina although Aβ has been isolated in aged human retinas [132]. Research on the retinas of AD transgenic mice has demonstrated Aβ plaques, hyperphosphorylated tau, increased microvascular deposition of Aβ and neuroinflammation [133][134]. Aβ immunotherapy in such transgenic mice has resulted in the clearance of retinal plaques but an increase in retinal amyloid angiopathy, identifying non-invasive retinal imaging as an alternative method for monitoring disease response to immunotherapy in these mice.…”

Section: (Figure 4)mentioning

confidence: 99%

“…Aβ plaques as well as retinal microvascular deposition of Aβ have been identified in the retinas of AD transgenic mouse models [133] and could possibly be detected by non-invasive optical scattering [110], Raman spectroscopic or fluorescent tagging techniques. Given the homology between the retinal and cerebral microvasculatures [148], it is not unexpected that changes in the retinal vasculature might also occur in AD.…”

Section: (Figure 7)mentioning

confidence: 99%

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Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

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Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a progressive decline in memory, learning and executive function and neuropathologically by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive pre-mortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred, hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments.While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular based screening test for AD.

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Section: (Figure 7)mentioning

confidence: 99%

Section: (Figure 4)mentioning

confidence: 99%

Section: (Figure 7)mentioning

confidence: 99%

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Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

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“…The neuropathological hallmarks have been confirmed in the retina using transgenic mouse models of AD. Whole mount retinae of transgenic mice have demonstrated beta-amyloid structures in the retina (Ning et al 2008;Liu et al 2009;Peterz et al 2009) 32 . Histological examination of the retinal cross sections reveals elevated amyloid plaques in the RGCs, RNFL and superficial retinal layers (Ning et al 2008;Peterz et al 2009) 33 .…”

Section: Studies In Animal Modelsmentioning

confidence: 99%

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Mahajan

Votruba

2017

Acta Ophthalmologica

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Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of senile dementia. It impairs the quality of life of a person and their family, posing a serious economic and social threat in developed countries. The fact that the diagnosis can only be definitively made post‐mortem, or when the disease is fairly advanced, presents a serious problem if novel therapeutic interventions are to be devised and used early in the course of the disease. There is therefore a pressing need for more sensitive and specific diagnostic tests with which we can detect AD in the preclinical stage. The tau proteins and beta‐amyloid proteins start to accumulate 20 years before the symptoms begin to manifest. Detecting them in the preclinical stage would be a potential breakthrough in the management of AD. A high degree of clinical suspicion is needed to correlate problems in cognition with the changes in the eye, particularly the retina, pupil and ocular movements, so that the disease can be detected early and managed in the prodromal phase. In this systematic review, we ask the question whether the retina can be used to make a specific and early diagnosis of AD.

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“…68 Furthermore, AB plaques, hyperphosphorylated tau, and retinal microvascular neuro-inflammation have been identified in the retinas of AD transgenic mice. 69,70 The main ocular biomarker investigated for AD has been thinning of the RNFL, as this may reflect both generalised neurodegeneration and local involvement, and this is reviewed below. Other ocular biomarkers investigated in AD include pupillary abnormalities: hypersensitivity to pupillary dilatation with cholinergic antagonist eye drops, [71][72][73] supersensitive pupillary response to cholinergic agonists, 74 and altered pupil flash responses.…”

Section: The Eye In Admentioning

confidence: 99%

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Jones-Odeh

Hammond

2015

Eye

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Glaucoma is a neurodegenerative disorder with established relationships with ocular structures such as the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). Ocular imaging techniques such as optical coherence tomography (OCT) allow for quantitative measurement of these structures. OCT has been used in the monitoring of glaucoma, as well as investigating other neurodegenerative conditions such as Alzheimer's disease (AD) and multiple sclerosis (MS). In this review, we highlight the association between these disorders and ocular structures (RNFL and GCL), examining their usefulness as biomarkers of neurodegeneration. The average RNFL thickness loss in patients with AD is 11 μm, and 7 μm in MS patients. Most of the studies investigating these changes are cross-sectional. Further longitudinal studies are required to assess sensitivity and specificity of these potential ocular biomarkers to neurodegenerative disease progression. Eye (2015Eye ( ) 29, 1270Eye ( -1284 doi:10.1038/eye.2015; published online 4 September 2015 IntroductionGlaucoma is a neurodegenerative optic neuropathy manifesting with progressive retinal ganglion cell (RGC) and axonal loss, which can result in visual field defects and blindness because of permanent cellular and neuronal damage. Subjective clinical examination of the optic nerve head (ONH) allows for assessment and monitoring of the structural changes associated with glaucoma. However, objective detection of defects in the peripapillary retinal nerve fibre layer (RNFL) by ophthalmoscopy is difficult. The relationship between glaucoma progression and the structural changes observed at the ONH, RGC layer, and RNFL in glaucoma is well established. [1][2][3][4] Early diagnosis and treatment of glaucoma is vital to maintain visual field, as loss of RGCs is irreversible, 5 and even before any detectable visual field defects, there is a substantial loss of RGCs. Morphological abnormalities can develop 3-5 years before any functional loss is detected. 6 Since the introduction of ocular imaging techniques such as optical coherence tomography (OCT), peripapillary RNFL thickness measurements have been used for the detection and monitoring of glaucoma. 7,8 However, the use of OCT has extended beyond RNFL measurements for glaucoma, and has also been used in the investigation of other neurodegenerative disorders such as Alzheimer's disease (AD) 9-11 and multiple sclerosis (MS). [12][13][14] In addition, given the similarities of brain and retinal foetal angiogenesis, 15,16 retinal microvasculature has also been investigated as a biomarker of changes in cerebral vasculature and cognitive decline. [17][18][19] In this review, we examine the relationships between glaucoma, neurodegenerative disease, and cognitive impairment, and the use of RNFL thickness and RGC loss as potential ocular biomarkers for neurodegenerative disorders such as AD and MS. We review the strength of associations between RNFL and RGC and Eye (2015Eye ( ) 29, 1270Eye ( -1284Eye ( © 2015 Macmillan Publis...

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Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer’s Transgenic Mice

Cited by 159 publications

References 70 publications

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

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