Selected Publications

Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model

Lee E. Goldstein, Andrew M. Fisher, Chad A. Tagge, Xiao-Lei Zhang, Libor Velisek, John A. Sullivan, Chirag Upreti, Jonathan M. Kracht, Maria Ericsson, Mark W. Wojnarowicz, Cezar J. Goletiani, Giorgi M. Maglakelidze, Noel Casey, Juliet A. Moncaster, Olga Minaeva1, Robert D. Moir, Christopher J. Nowinski, Robert A. Stern, Robert C. Cantu, James Geiling, Jan K. Blusztajn, Benjamin L. Wolozin, Tsuneya Ikezu, Thor D. Stein, Andrew E. Budson, Neil W. Kowall, David Chargin, Andre Sharon, Sudad Saman, Garth F. Hall, William C. Moss, Robin O. Cleveland, Rudolph E. Tanzi, Patric K. Stanton and Ann C. McKee
SciTranslMed 16 May 2012: Vol.4, Issue 134,p.134ra60


© 2012 SciTranslMed
The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

Craddock Travis J.A., Tuszynski1 Jack A., Chopra Deepak, Casey Noel, Goldstein Lee E., Hameroff Stuart R., Tanzi Rudolph E.
PLoS One. March 2012;7(3):e33552.


© 2012 PLoS One
15 kDa selenoprotein (Sep15) knockout mice: roles of Sep15 in redox homeostasis and cataract development

Kasaikina MV, Fomenko DE, Labunskyy VM, Lachke SA, Qiu W, Moncaster JA, Zhang J, Wojnarowicz MW Jr, Natarajan SK, Malinouski M, Schweizer U, Tsuji PA, Carlson BA, Maas RL, Lou MF, Goldstein LE, Hatfield DL, Gladyshev VN.
J Biol Chem. 2011 Jul 18. [Epub ahead of print], PMID: 21768092 [PubMed - as supplied by publisher]


Related Citations:

© 2011 J Biol Chem
Demand for Zn in Acid-secreting gastric mucosa and its requirement for intracellular Ca

Liu J, Kohler JE, Blass AL, Moncaster JA, Mocofanescu A, Marcus MA, Blakely EA, Bjornstad KA, Amarasiriwardena C, Casey N, Goldstein LE, Soybel DI.
PLoS One. 2011;6(6):e19638. Epub 2011 Jun 15, PMID: 21698273 [PubMed - in process]


Related Citations:

© 2011 PLoS One
Alzheimer's Diesease Amyloid-β Links Lens and Brain Pathology in Down Syndrome

Juliet A. Moncaster, Roberto Pineda, Robert D. Moir, Suqian Lu, Mark A. Burton, et al.
PLoS ONE 2010, Volume 5, Issue 5, e10659


© 2010 PLos One
The Alzheimer’s Disease-Associated Amyloid-β Protein is an Antimicrobial Peptide

Stephanie J. Soscia1, James E. Kirby, Kevin J. Washicosky1, Stephanie M. Tucker1, Martin Ingelsson, Bradley Hyman1, Mark A. Burton, Lee E. Goldstein, Scott Duong, Rudolph E. Tanzi1, Robert D. Moir
PLoS ONE 2010, Volume 5, Issue 3, e9505


© 2010 PLos One
Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease

Lee E Goldstein, Julien A Muffat, Robert A Cherny, Robert D Moir, Maria H Ericsson, Xudong Huang, Christine Mavros, Jennifer A Coccia, Kyle Y Faget, Karlotta A Fitch, Colin L Masters, Rudolph E Tanzi, Leo T Chylack Jr, Ashley I Bush
Lancet 2003, 361, 1258—1265
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Background: Pathological hallmarks of Alzheimer's disease include cerebral β-amyloid (Aβ) deposition, amyloid accumulation, and neuritic plaque formation. We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain.

Methods: We obtained postmortem specimens of eyes and brain from nine individuals with Alzheimer's disease and eight controls without the disorder, and samples of primary aqueous humour from three people without the disorder who were undergoing cataract surgery. Dissected lenses were analysed by slit-lamp stereophotomicroscopy, western blot, tryptic-digest/mass spectrometry electrospray ionisation, and anti-Aβ surface-enhanced laser desorption ionisation (SELDI) mass spectrometry, immunohistochemistry, and immunogold electron microscopy. Aqueous humour was analysed by anti-Aβ SELDI mass spectrometry. We did binding and aggregation studies to investigate Aβ-lens protein interactions.

Findings: We identified Aβ—140 and Aβ1—42 in lenses from people with and without Alzheimer's disease at concentrations comparable with brain, and Aβ1—40 in primary aqueous humour at concentrations comparable with cerebrospinal fluid. Aβ accumulated in lenses from individuals with Alzheimer's disease as electron-dense deposits located exclusively in the cytoplasm of supranuclear/deep cortical lens fibre cells (n=4). We consistently saw equatorial supranuclear cataracts in lenses from people with Alzheimer's disease (n=9) but not in controls (n=8). These supranuclear cataracts colocalised with enhanced Aβ immunoreactivity and birefringent Congo Red staining. Synthetic Aβ bound αB-crystallin, an abundant cytosolic lens protein. Aβ promoted lens protein aggregation that showed protofibrils, birefringent Congo Red staining, and Aβ/αB-crystallin coimmunoreactivity.

Interpretation: Aβ is present in the cytosol of lens fibre cells of people with Alzheimer's disease. Lens Aβ might promote regionally-specific lens protein aggregation, extracerebral amyloid formation, and supranuclear cataracts.

© 2003 The Lancet Publishing Group
3-Hydroxykynurenine and 3-Hydroxyanthranilic Acid Generate Hydrogen Peroxide and Promote α-Crystallin Cross-Linking by Metal Ion Reduction

Lee E. Goldstein, Michael C. Leopold, Xudong Huang, Craig S. Atwood, Aleister J. Saunders, Mariana Hartshorn, James T. Lim, Kyle Y. Faget, Julien A. Muffat, Richard C. Scarpa, Leo T. Chylack, Jr., Edmond F. Bowden, Rudolph E. Tanzi, and Ashley I. Bush
Biochemistry 2000, 39, 7266—7275
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The kynurenine pathway catabolite 3-hydroxykynurenine (3HK) and redox-active metals such as copper and iron are implicated in cataractogenesis. Here we investigate the reaction of kynurenine pathway catabolites with copper and iron, as well as interactions with the major lenticular structural proteins, the α-crystallins. The o-aminophenol kynurenine catabolites 3HK and 3-hydroxyanthranilic acid (3HAA) reduced Cu(II)>Fe(III) to Cu(I) and Fe(II), respectively, whereas quinolinic acid and the nonphenolic kynurenine catabolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAA generated superoxide and hydrogen peroxide in a copper-dependent manner. In addition, 3HK and 3HAA fostered copper-dependent R-crystallin cross-linking. 3HK- or 3HAA-modifed R-crystallin showed enhanced redox activity in comparison to unmodified R-crystallin or ascorbate-modified α-crystallin. These data support the possibility that 3HK and 3HAA may be cofactors in the oxidative damage of proteins, such as α-crystallin, through interactions with redox-active metals and especially copper. These findings may have relevance for understanding cataractogenesis and other degenerative conditions in which the kynurenine pathway is activated.

© 2000 American Chemical Society