Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease

Goldstein, Lee E.; Muffat, Julien; Cherny, Robert A.; Moir, Robert D.; Ericsson, Maria; Huang, Xudong; Mavros, Christine; Coccia, Jennifer A.; Fagét, Kyle Y.; Fitch, Karlotta A.; Masters, Colin L.; Tanzi, Rudolph E.; Chylack, Leo T.; Bush, Ashley I.

doi:10.1016/s0140-6736(03)12981-9

Cited by 333 publications

(328 citation statements)

References 26 publications

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“…Remarkably, research indicates that a particular type of cataract (equatorial supranuclear cataract) might be specific to AD sufferers [106]. Slit-lamp microscopy of ex-vivo intra-ocular lenses of individuals with AD consistently revealed equatorial supranuclear cataracts.…”

Section: (Figure 3)mentioning

confidence: 99%

“…This high protein concentration, along with the optical accessibility of the lens, makes it ideal for the optical investigation of protein aggregation in disease, in vivo. The Aβ protein involved in the pathogenesis of AD in the brain has also been found to exist in the lens (Aβ40 and Aβ42), aqueous humor (Aβ40) and vitreous humor (Aβ42) of the normal human eye [106][107].…”

Section: The Ocular Lens and Vitreous Humor In Alzheimer's Diseasementioning

confidence: 99%

“…For early diagnosis of AD, it has been proposed that a suitable eye-drop biomarker may enable Aβ in the anterior chamber to be stained and quantified [106]. Alternatively, the size of Aβ aggregates in the eye may facilitate non-invasive detection with optical scattering [110], spectral or autofluorescence techniques.…”

Section: (Figure 3)mentioning

confidence: 99%

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Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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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 3)mentioning

confidence: 99%

Section: The Ocular Lens and Vitreous Humor In Alzheimer's Diseasementioning

confidence: 99%

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Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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“…Goldstein et al [79] measured b-amyloid 1-40 (Ab 1-40) levels in the aqueous humor of Alzheimer patients with antiAb SELDI-TOF chips.…”

Section: Biomarker Profiling: Seldi-tof and Clinprot Maldi-tofmentioning

confidence: 99%

Proteomics in ocular fluids

Grus

Joachim

Pfeiffer

2007

Proteomics Clinical Apps

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The focus of this article is to review recent techniques in proteomic analysis of ocular fluids. These fluids include tears, aqueous humor, and vitreous, they will also be compared to serum analysis. Furthermore, we attempt to summarize some disease correlated biomarkers in ocular fluids that were discovered through different proteomic techniques in eye diseases like dry eye, glaucoma, age-related macular degeneration, uveitis, or diabetic retinopathy. This review is trying to point out the importance of these biomarkers for clinical applications.

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“…pilocarpine) drugs [59][60][61][62][63][64][65][66][67]. Some have even proposed that this altered response could be pathognomonic of AD [68][69][70][71] while others have refuted this hypothesis as non-specific [72].The crystalline lens also could be involved in AD, and high levels of β-amyloid were described in lens epithelia of subjects with a particular and rare type of cataract, the anterior subcapsular cataract [73,74] in the number of optic nerve fibers, probably due to the toxicity on RGCs of β-amyloid, has been detected in some studies [78][79][80]. …”

mentioning

confidence: 99%

Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

Pescosolido¹,

Pascarella²,

Buomprisco³

et al. 2014

AOVS

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two distinct pathologies, despite similar pathophysiology and demographic distribution. Both diseases are neurodegenerative, chronic and progressive in nature, with irreversible neuronal cell loss. Furthermore, both POAG and AD disease primarily affect the elderly, with a strongly age-dependent incidence. The progressive debilitating course of both diseases has tremendous implications on an aging population [1]. For years Glaucoma has been associated with high IOP [2], although scientists had accepted this etiology with caution, since it was known that POAG could develop in subjects with normal or even low IOP. In fact, one out of three POAG patients has normotensive or low tension glaucoma [3]. This observation has led the scientific community to look for other possible causes of this slowly debilitating pathogenesis.The hallmark of neurodegenerative diseases is the death of specific neuron populations, and of those other neurons that are inter-connected and depend for their survival on the inputs from the main population (trans-synaptic degeneration). In Parkinson's disease accumulation of alfa-synuclein [4] causes the degeneration of dopaminergic neurons of the substantia nigra, in the midbrain, thus leading to the classic symptoms of Parkinson's such as tremor, akinesia, bradykinesia, and stiffness [5]. In AD there is a loss of neurons in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus [6]. Both amyloid plaques and neurofibrillary tangles are AbstractA third of people affected by primary open angle glaucoma (POAG) have normal or even low intraocular pressure (IOP), such as in the case of normotensive glaucoma and low pressure glaucoma. Therefore, high IOP, while remaining the most important risk factor for POAG development, is not the only one. POAG has been recognized to belong to the class of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's, and several recent studies have suggested possible links between Alzheimer's and glaucoma both from an epidemiological and a pathogenetic point of view. In fact, several pathogenetic factors are common between the two diseases: the diffuse axonal degeneration of ganglion cells, the presence of specific markers (such as amyloid-β) in the aqueous humor, the activation of caspases and the abnormal processing of amyloid precursor protein in retinal ganglion cells, the reduction of the intracranial pressure of the cerebrospinal fluid, the mutations of the gene that encodes for optineurine. Conflicting data have been reported concerning apolipoprotein E. Finally, numerous publications affirm the utility of molecules traditionally used in the treatment of neurodegenerative diseases (e.g. forskolin, L-carnosine, homotaurine, folic acid, acetylcholinesterase inhibitors, antioxidant vitamins, glatiramer acetate, etc.) also in the treatment of glaucoma.In the present research we ana...

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Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease

Cited by 333 publications

References 26 publications

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Proteomics in ocular fluids

Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

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