May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Beta–Amyloid Lens Pathology and Alzheimer's–Like Equatorial Supranuclear/Deep Cortical Cataracts in Down's Syndrome (Trisomy 21)
Author Affiliations & Notes
  • L.E. Goldstein
    Brigham & Women's Hospital, Harvard Medical School, Boston, MA
    Molecular Aging & Development Lab, Center for Ophthalmic Research,
  • R. Pineda
    Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA
  • D.G. Hunter
    Children's Hospital, Harvard Medical School, Boston, MA
  • S. Lu
    Brigham & Women's Hospital, Harvard Medical School, Boston, MA
    Molecular Aging & Development Lab, Center for Ophthalmic Research,
  • R.D. Moir
    Genetics & Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA
  • J. Moncaster
    Brigham & Women's Hospital, Harvard Medical School, Boston, MA
    Molecular Aging & Development Lab, Center for Ophthalmic Research,
  • R.D. Folkerth
    Brigham & Women's Hospital, Harvard Medical School, Boston, MA
    Dept of Pathology,
  • R.M. Robb
    Children's Hospital, Harvard Medical School, Boston, MA
  • R.E. Tanzi
    Genetics & Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA
  • L.T. Chylack, Jr.
    Brigham & Women's Hospital, Harvard Medical School, Boston, MA
    Molecular Aging & Development Lab, Center for Ophthalmic Research,
  • Footnotes
    Commercial Relationships  L.E. Goldstein, None; R. Pineda, None; D.G. Hunter, None; S. Lu, None; R.D. Moir, None; J. Moncaster, None; R.D. Folkerth, None; R.M. Robb, None; R.E. Tanzi, None; L.T. Chylack, None.
  • Footnotes
    Support  L.Goldstein: NIGMS (RO1–GM75986), NIA/AFAR (Beeson Scholar, K23–AG024792 HIGHWIRE EXLINK_ID="47:5:2532:1" VALUE="AG024792" TYPEGUESS="GEN" /HIGHWIRE ), Alz Assoc, MA Lion's Eye Res Fund, USDA/CSREES, two anonymous foundations.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 2532. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose:
 

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.

 
Methods:
 

Slit lamp photomicroscopy, immunohistochemistry, ELISA, western blot, protein sequencing.

 
Results:
 

DS patients express early–onset equatorial supranuclear/deep cortical cataracts that co–localize with lenticular Aß deposition and ß–amyloid pathology.

 
Conclusions:
 

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: lgoldstein@rics.bwh.harvard.edu.  

 
Keywords: cataract • pathobiology • aging 
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