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P2‐230: High‐resolution multi‐elemental metallomic mapping of the human eye in Alzheimer's disease and normal aging
Author(s) -
Casey Noel,
Moncaster Juliet,
Connelly Timothy,
Wojnarowicz Mark,
Fraine Andrew,
Minaeva Olga,
Sarangi Srikant,
Goldstein Lee
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1114
Subject(s) - retinal , high resolution , chemistry , ophthalmology , medicine , geology , remote sensing
Background:We previously identified amyloid-b (Ab) deposition, amyloid pathology, and co-localizing supranuclear cataracts in the lens of the eye in Alzheimer’s disease (AD) and Down Syndrome (DS) [Goldstein, 2003; Moncaster, 2010]. Interaction of Ab and biometals represents a major pathogenic pathway in AD and provides the basis for clinical effective disease-modifying therapy (Duce and Bush, 2010; Lannfelt, 2008). To date, mapping the ocular metallome has been limited by technical barriers. Here we developed a new technique, High-Resolution Metallomic Imaging Mass Spectrometry (HR-MIMS), to perform the first high-resolution multielemental and isotopic distribution maps of the metallome of the adult human eye in AD and age-matched controls. Methods: Human eyes were obtained through the Boston University Alzheimer’s Disease Center and NDRI (Philadelphia, PA). Eyes were flash frozen and analyzed by metallomic imagingmass spectrometry (MIMSmapping) using a custom cryogenic cell coupled to nanosecond ultraviolet laser ablation (NULA) and hyphenated high-resolution magnetic sector field ICP-MS at the Boston University Center for Biometals & Metallomics, Boston, MA. Laser wavelength, 213 nm; rate, 5-50 mms-1; spot size: 10 micron (high resolution) to 100 micron (scanning resolution). MIMS analysis was conducted on surround to establish elemental background and calibrated with NIST standards. Results: High resolutionmetallomic maps generated fromAD and age-matched control eyes demonstrated unique elemental and isotopic distribution patterns. Zinc was confirmed in the subequatorial supranucleus of the lens, the same region implicated in AD-linked Ab accumulation and cataractogenesis. Retinal zinc demonstrated a laminar distribution corresponding to cytoarchitectonic organization. Retinal iron revealed a vascular distribution pattern. Simultaneous metallomic maps of the same lenses revealed distinctive elemental and isotopic distribution patterns for other important biometals, including copper (Cu), iron (Fe), selenium (Se), molybdenum (Mo), manganese (Mn), and other elements. Conclusions: We deployed HR-MIMS analysis to generate detailed quantitative high-resolution spatial distribution maps of essential and trace elements and isotopes in adult human eyes in AD and age-matched controls at 10-100 micron spatial resolution. This study strongly supports a role for zinc in AD-linked lens pathology.