March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Characterization And Modulation of Alzheimer’s Disease Amyloid-β (Aβ) Protein Aggregation Monitored By Quasi-elastic Light Scattering (QLS)
Author Affiliations & Notes
  • Juliet A. Moncaster
    School of Medicine,
    Boston University, Boston, Massachusetts
  • Srikant Sarangi
    Biomedical Engineering,
    Boston University, Boston, Massachusetts
  • Olga Minaeva
    Biomedical Engineering,
    Boston University, Boston, Massachusetts
  • Noel Casey
    School of Medicine,
    Boston University, Boston, Massachusetts
  • Maria Ericsson
    Electron Microscopy Facility, Dept Cell Biology, Harvard Medical School, Boston, Massachusetts
  • Mark Wojnarowicz
    School of Medicine,
    Boston University, Boston, Massachusetts
  • Robin Altman
    University of California-Davis, Davis, California
  • John I. Clark
    Biological Structure and Ophthalmology, University of Washington, Seattle, Washington
  • John C. Voss
    University of California-Davis, Davis, California
  • Lee E. Goldstein
    School of Medicine,
    Boston University, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Juliet A. Moncaster, None; Srikant Sarangi, None; Olga Minaeva, None; Noel Casey, None; Maria Ericsson, None; Mark Wojnarowicz, None; Robin Altman, None; John I. Clark, None; John C. Voss, None; Lee E. Goldstein, Neuroptix, Corp. (C, P)
  • Footnotes
    Support  NIH-NIGMS, NIH-NIA P30-AG13846, DOE, NASA
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3026. doi:https://doi.org/
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      Juliet A. Moncaster, Srikant Sarangi, Olga Minaeva, Noel Casey, Maria Ericsson, Mark Wojnarowicz, Robin Altman, John I. Clark, John C. Voss, Lee E. Goldstein; Characterization And Modulation of Alzheimer’s Disease Amyloid-β (Aβ) Protein Aggregation Monitored By Quasi-elastic Light Scattering (QLS). Invest. Ophthalmol. Vis. Sci. 2012;53(14):3026. doi: https://doi.org/.

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

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Abstract

Purpose: : Alzheimer’s disease (AD) is characterized by age-related cerebral deposition of amyloid-β peptides (Aβ). We discovered that Aβ accumulates in the supranuclear region of the lens in patients with AD (Goldstein, 2003) and Down Syndrome (DS) (Moncaster, 2010), a common chromosomal disorder that carries 100% risk of early-onset AD. In AD and DS lenses, Aβ accumulates as electron-dense intracellular aggregates 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 AD-specific supranuclear lens cataracts. Aβ aggregates can be generated in vitro by controlled incubation of human lens protein extract with synthetic Aβ peptide. We are investigating the properties and mechanisms of age-related changes and Aβ protein aggregation by modeling constituent molecular interactions in vitro.

Methods: : Quasi-Elastic Light Scattering (QLS) analyzes time-dependent light scattering intensity fluctuations from which autocorrelation functions can be derived. The autocorrelation function supplies quantitative information about the molecular size and mobility of the sampled light scattering particles The instrument utilizes a low power near infrared laser (0.3 mW; = 780 nm) as a light source, an avalanche photodiode to detect scattered photons, and an autocorrelator with a sampling time of 480 ns to provide an analytical detection range of ~10 nm to ~100 nm when assessed using polystyrene beads. Electron Paramagnetic Resonance (EPR) is used to understand further the interaction of Aβ and αB-crystallin.

Results: : Our studies have revealed an interaction of Aβ and αB-crystallin in the lens that is also present in neuritic and diffuse plaque in AD brain. These results demonstrate that our QLS instrument is capable of detecting and differentiating molecular states that we predicted would correspond to early AD-associated lens Aβ accumulation in vivo. Hetero-oligomeric interaction of Aβ and αB-crystallin can be detected, monitored and modeled using data derived from complementary QLS and EPR analyses.

Conclusions: : We have demonstrated interactions between Aβ and αB-crystallin that can be modulated in vitro. These findings have implications for understanding AD pathogenesis.

Keywords: pathology: experimental • crystallins • protein structure/function 
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