April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Non-Invasive Detection of Age-Related and Alzheimer's Disease Linked Pathology in the Lenses of Human Subjects with Down Syndrome
Author Affiliations & Notes
  • Srikant Sarangi
    Biomedical Engineering, Boston University, Boston, MA
  • Olga Minaeva
    Biomedical Engineering, Boston University, Boston, MA
    Boston School of Medicine, Boston University, Boston, MA
  • Juliet A Moncaster
    Boston School of Medicine, Boston University, Boston, MA
  • Caitlin Rook
    Ophthalmology, Boston Children, Boston, MA
  • Frank Weng
    Ophthalmology, Boston Children, Boston, MA
  • Danielle M Ledoux
    Ophthalmology, Boston Children, Boston, MA
  • David G Hunter
    Ophthalmology, Boston Children, Boston, MA
  • Lee E Goldstein
    Biomedical Engineering, Boston University, Boston, MA
    Boston School of Medicine, Boston University, Boston, MA
  • Footnotes
    Commercial Relationships Srikant Sarangi, None; Olga Minaeva, None; Juliet Moncaster, None; Caitlin Rook, None; Frank Weng, None; Danielle Ledoux, None; David Hunter, REBIScan (C), REBIScan (I), REBIScan (P); Lee Goldstein, The Brigham and Women's Hospital, Inc. (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 6024. doi:https://doi.org/
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    • Get Citation

      Srikant Sarangi, Olga Minaeva, Juliet A Moncaster, Caitlin Rook, Frank Weng, Danielle M Ledoux, David G Hunter, Lee E Goldstein; Non-Invasive Detection of Age-Related and Alzheimer's Disease Linked Pathology in the Lenses of Human Subjects with Down Syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6024. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The hallmark pathology in Alzheimer’s disease (AD) and Down syndrome is characterized by age-related deposition in the brain of amyloid β peptides (Aβ), which eventually results in plaque formation. Aβ is a cleavage product derived from the amyloid precursor protein (APP). We discovered that Aβ also accumulates in the supranuclear region of the lens in patients with AD (Goldstein et al., Lancet, 2003) and Down Syndrome (DS) (Moncaster et al., PloS One, 2010). DS is a common chromosomal disorder that carries 100% risk of early-onset AD and is the leading genetic cause of intellectual disability in humans. Triplication of chromosome 21 in DS invariably includes the APP gene (21q21) resulting in increased expression of APP and consequently Aβ.

Methods: In AD and DS lenses, Aβ accumulates as electron-dense intracellular aggregates (~5-100 nm) that distribute heterogeneously within the cytoplasm of supranuclear and deep cortical lens fiber cells. These Aβ lens aggregates qualify as Raleigh scattering centers that clinically manifest as distinctive specific supranuclear lens opacities and are phenotypically, anatomically, and biochemically distinguishable from common age-related nuclear cataracts. Here, we use Quasi-elastic Light Scattering (QLS) to detect and monitor these changes both in vitro and in vivo.

Results: Age-related and amyloid beta linked changes were observed in protein solutions and in an amyloid beta over-expression transgenic mouse model. Moreover we present preliminary results that suggest differences between DS patients and age-matched controls.

Conclusions: Changes in protein solutions can be attributed to post-translational modifications which occur over time and with other physiologically relevant perturbations. In the mouse model, we see differences between the transgenic mice compared to age-matched wild-type controls due to the over-expression of amyloid beta. Finally, from the initial results of the human clinical study there appear to be differences in particle characteristics between DS and control patients, and this will be explored further in future studies.

Keywords: 413 aging • 657 protein modifications-post translational  
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