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L.E. Goldstein, R. Pineda, D.G. Hunter, S. Lu, R.D. Moir, J. Moncaster, R.D. Folkerth, R.M. Robb, R.E. Tanzi, L.T. Chylack, Jr.; Beta–Amyloid Lens Pathology and Alzheimer's–Like Equatorial Supranuclear/Deep Cortical Cataracts in Down's Syndrome (Trisomy 21) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2532.
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We previously reported ß–amyloid (Aß) deposition, ß–amyloid pathology, and co–localizing supranuclear cataracts in Alzheimer's disease (AD), the first evidence of AD–associated ß–amyloid pathology outside the brain (Goldstein et. al., Lancet, 2003). Down's Syndrome (DS, Trisomy 21) is a chromosomal disorder associated with fully–penetrant, early–onset AD. DS results from triplication of the Ch21 DSCR region containing the ß–amyloid precursor protein (ß–APP) gene. DSCR locus triplication is associated with Aß overexpression, AD–associated neuropathology, and invariant early–onset AD. Intriguingly, DS patients also express a highly penetrant, early–onset cataract phenotype that is strikingly similar to that observed in late–onset AD. Here we present results of an ongoing study to characterize the DS cataract phenotype, identify the underlying molecular pathology, and establish a genotype–phenotype relationship linking AD–associated Aß overexpression and supranuclear/deep cortical cataractogenesis.
Slit lamp photomicroscopy, immunohistochemistry, ELISA, western blot, protein sequencing.
DS patients express early–onset equatorial supranuclear/deep cortical cataracts that co–localize with lenticular Aß deposition and ß–amyloid pathology.
DS patients express an early–onset equatorial supranuclear/deep cortical cataract phenotype and co–localizing ß–amyloid molecular pathology similar to that observed in AD. These findings: (1) identify candidate molecular pathology for DS cataract development, (2) establish a genotype–phenotype relationship linking AD–associated Aß accumulation and supranuclear/deep cortical cataractogenesis, and (3) provide further support for systemic pathogenesis and lenticular phenotypic expression in AD. Correspondence: firstname.lastname@example.org.
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