Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease

Ning, Allison; Cui, Jing; To, Eleanor; Ashe, Karen H.; Matsubara, Joanne A.

doi:10.1167/iovs.08-1849

Cited by 268 publications

(305 citation statements)

References 52 publications

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“…By analogy, the lack of human APP transgene expression in the periphery in APP23 mice may be responsible for the failure of ␤-amyloid induction after peripheral inoculations. Although this possibility cannot be ruled out, the absence of amyloid induction after intraocular and intranasal administration argues against it, because both the retina and the olfactory bulb, as components of the CNS, express the human APP protein in APP transgenic mice using neuronal promoters (37,38).…”

Section: Discussionmentioning

confidence: 99%

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

Eisele

Bolmont

Heikenwälder

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

262

248

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Despite the importance of the aberrant polymerization of A␤ in the early pathogenic cascade of Alzheimer's disease, little is known about the induction of A␤ aggregation in vivo. Here we show that induction of cerebral ␤-amyloidosis can be achieved in many different brain areas of APP23 transgenic mice through the injection of dilute A␤-containing brain extracts. Once the amyloidogenic process has been exogenously induced, the nature of the induced A␤-deposition is determined by the brain region of the host. Because these observations are reminiscent of a prion-like mechanism, we then investigated whether cerebral ␤-amyloidosis also can be induced by peripheral and systemic inoculations or by the intracerebral implantation of stainless steel wires previously coated with minute amounts of A␤-containing brain extract. Results reveal that oral, intravenous, intraocular, and intranasal inoculations yielded no detectable induction of cerebral ␤-amyloidosis in APP23 transgenic mice. In contrast, transmission of cerebral ␤-amyloidosis through the A␤-contaminated steel wires was demonstrated. Notably, plasma sterilization, but not boiling of the wires before implantation, prevented the induction of ␤-amyloidosis. Our results suggest that minute amounts of A␤-containing brain material in direct contact with the CNS can induce cerebral ␤-amyloidosis, but that systemic cellular mechanisms of prion uptake and transport to the CNS may not apply to A␤.Alzheimer's disease ͉ amyloid ͉ prion ͉ sterilization ͉ transmission

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Section: Discussionmentioning

confidence: 99%

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

Eisele

Bolmont

Heikenwälder

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

262

248

View full text Add to dashboard Cite

show abstract

“…Double transgenic mouse models have supported these findings, with RGCs undergoing apoptosis and APP deposition occurring in the GCL and inner nuclear layer. 101 Other studies of human tau transgenic mice 79 have reported accumulations of hyperphosphorylated transgenic tau in the RNFL and RGCs. Other transgenic mice models have suggested that the inner plexiform layer may be a more sensitive biomarker for detecting AD-related changes compared with RGCs, 70,80 making it difficult to draw firm conclusions.…”

Section: The Ganglion Cell Layer 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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“…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%

“…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 . Using retinal imaging techniques, plaque formation and clearance following immunotherapy, in which altered myelin antigen is loaded on dendritic cells, can be used in vivo and can be used to demonstrate the progress of the disease.…”

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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Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease

Cited by 268 publications

References 52 publications

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

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

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

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