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N. F. Casey, J. A. Moncaster, O. Mineva, M. Burton, A. Fraine, S. Sarangi, L. E. Goldstein; Mapping the Lens Metallome in Normal Aging and Alzheimer’S Disease by Laser Ablation Sector Field Inductively Coupled Mass Spectrometry (LA-SF-ICP-MS). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4587.
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We previously identified amyloid-β (Aβ) deposition, amyloid pathology, and co-localizing subequatorial supranuclear cataracts in Alzheimer’s disease (AD; Goldstein et al. Lancet, 2003). Aβ aggregation in the brain is a cardinal feature of AD pathogenesis. In AD lens, Aβ aggregates as hetero-oligomeric complexes that localize to the cytosol of supranuclear fiber cells. Emerging evidence indicates that metals bind to and promote Aβ aggregation. Accurately determining the spatial distribution of trace metals in lens and brain will facilitate elucidation of pathogenic metalloprotein interactions in affected tissues. Here we utilize state-of-the-art laser ablation sector field inductively coupled mass spectrometry (LA-SF-ICP-MS) to generate high-resolution ultra-trace elemental and isotopic spatial distribution maps of the adult human lens metallome in AD and aged control lenses.
Lens specimens were procured through national tissue networks (National Disease Registry Interchange, Philadelphia; PA). Tissue specimens were dissected, flash frozen, and analyzed by ns-ultraviolet laser ablation hyphenated to a Element-XR SF-ICP-MS. Laser ablation parameters: 213nm; scan rate, 5-50µms-1; spot size, 10µm (high resolution) to 100µm (scanning mode). Scanning was initiated on the surrounding to establish elemental background.
Detailed high-resolution elemental and isotope maps generated from human lenses obtained from AD and aged control subjects demonstrate unique patterns of elemental and isotopic distribution for Cu, Zn, Ca, Mg, Na, P, Rb, C and S. Apparent age-related anatomical nuclear-to-cortical distribution patterns were observed for C and S compared to an apparent physiological epithelial-to-cortical pattern for Zn, Cu, Ca, Mg, P. Increased Zn was noted in the supranucleus and deep cortex of AD lenses, a finding consistent with our previous analyses using X-ray fluorescence microscopy.
LA-SF-ICP-MS was successfully used to generate high-resolution spatial distribution maps of the adult human lens metallome. This novel technique has accurately determined the distribution of physiologically active metals in the normal aged lens and confirms zinc dyshomeostasis in AD lenses. This study provides additional evidence pointing to Zn as a biometal contributor to amyloidogenic reactions and AD-linked pathology in the lens and brain.
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