William L Klein

Summary

Affiliation: Northwestern University
Country: USA

Publications

  1. ncbi request reprint Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets
    William L Klein
    Department of Neurobiology and Physiology, Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Institute for Neuroscience, 2153 North Campus Drive, 60208, Evanston, IL, USA
    Neurochem Int 41:345-52. 2002
  2. ncbi request reprint Amyloid beta oligomers induce impairment of neuronal insulin receptors
    Wei Qin Zhao
    Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Dr, Hogan 5 110, Evanston, IL 60280, USA
    FASEB J 22:246-60. 2008
  3. pmc Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 106:1971-6. 2009
  4. pmc Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}
    Wei Qin Zhao
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 284:18742-53. 2009
  5. pmc Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomers
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
    Neurobiol Aging 29:1334-47. 2008
  6. ncbi request reprint Targeting generation of antibodies specific to conformational epitopes of amyloid beta-derived neurotoxins
    Mary P Lambert
    Northwestern University, Dept of Neurobiology and Physiology, and the Cognitive Neurology and Alzheimer s Disease Center, Evanston, IL 60208, USA
    CNS Neurol Disord Drug Targets 8:65-81. 2009
  7. ncbi request reprint Monoclonal antibodies that target pathological assemblies of Abeta
    Mary P Lambert
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Neurochem 100:23-35. 2007
  8. ncbi request reprint Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 282:11590-601. 2007
  9. ncbi request reprint Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor
    Amanda J Haes
    Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 3113, USA
    J Am Chem Soc 127:2264-71. 2005
  10. ncbi request reprint Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease
    Pascale N Lacor
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Neurosci 27:796-807. 2007

Collaborators

Detail Information

Publications32

  1. ncbi request reprint Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets
    William L Klein
    Department of Neurobiology and Physiology, Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Institute for Neuroscience, 2153 North Campus Drive, 60208, Evanston, IL, USA
    Neurochem Int 41:345-52. 2002
    ..The properties of ADDLs and their presence in AD-afflicted brain are consistent with their putative role even in the earliest stages of AD, including forms of mild cognitive impairment...
  2. ncbi request reprint Amyloid beta oligomers induce impairment of neuronal insulin receptors
    Wei Qin Zhao
    Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Dr, Hogan 5 110, Evanston, IL 60280, USA
    FASEB J 22:246-60. 2008
    ....
  3. pmc Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 106:1971-6. 2009
    ..The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis...
  4. pmc Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}
    Wei Qin Zhao
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 284:18742-53. 2009
    ..Our results suggest that dysfunctions of brain insulin and IGF-1 receptors contribute to Abeta aggregation and subsequent synaptic loss...
  5. pmc Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomers
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
    Neurobiol Aging 29:1334-47. 2008
    ..A beta oligomers have been increasingly implicated as the main neurotoxins in AD, and the current results provide a unifying mechanism in which oligomer activity is directly linked to tau hyperphosphorylation in AD pathology...
  6. ncbi request reprint Targeting generation of antibodies specific to conformational epitopes of amyloid beta-derived neurotoxins
    Mary P Lambert
    Northwestern University, Dept of Neurobiology and Physiology, and the Cognitive Neurology and Alzheimer s Disease Center, Evanston, IL 60208, USA
    CNS Neurol Disord Drug Targets 8:65-81. 2009
    ..It can be anticipated that further development of such antibodies for use in clinical trials will come in the near future...
  7. ncbi request reprint Monoclonal antibodies that target pathological assemblies of Abeta
    Mary P Lambert
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Neurochem 100:23-35. 2007
    ....
  8. ncbi request reprint Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 282:11590-601. 2007
    ....
  9. ncbi request reprint Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor
    Amanda J Haes
    Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 3113, USA
    J Am Chem Soc 127:2264-71. 2005
    ....
  10. ncbi request reprint Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease
    Pascale N Lacor
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Neurosci 27:796-807. 2007
    ..The observed disruption of dendritic spines links ADDLs to a major facet of AD pathology, providing strong evidence that ADDLs in AD brain cause neuropil damage believed to underlie dementia...
  11. pmc Alzheimer's-associated Abeta oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal
    Jason Pitt
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    Toxicol Appl Pharmacol 240:189-97. 2009
    ..These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics...
  12. ncbi request reprint Synaptotoxic amyloid-β oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer's disease?
    William L Klein
    Cognitive Neurology and Alzheimer s Disease Center, Department of Neurobiology, Weinberg College of Arts and Science, Northwestern University, Evanston, IL 60208, USA
    J Alzheimers Dis 33:S49-65. 2013
    ..Although there still is no effective treatment for AD, insights over the past five years raise hopes that new approaches targeting Aβ oligomers could finally bring disease-modifying therapeutics...
  13. ncbi request reprint Femtomole immunodetection of synthetic and endogenous amyloid-beta oligomers and its application to Alzheimer's disease drug candidate screening
    Lei Chang
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    J Mol Neurosci 20:305-13. 2003
    ..The methods are suitable for screening combinatorial libraries and, importantly, provide the potential for simultaneous information on candidate transport across the blood-brain barrier...
  14. pmc Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease
    Dimitra G Georganopoulou
    Department of Chemistry and Institute of Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 102:2273-6. 2005
    ..This study is a step toward a diagnostic tool, based on soluble pathogenic markers for the debilitating disease...
  15. pmc Aβ oligomer-induced synapse degeneration in Alzheimer's disease
    Kyle C Wilcox
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    Cell Mol Neurobiol 31:939-48. 2011
    ..We also discuss ways in which mechanistic insights from other diseases offer clues in the pursuit of the molecular basis of Alzheimer's disease...
  16. ncbi request reprint Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1
    Masuo Ohno
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Eur J Neurosci 23:251-60. 2006
    ..Our gene-based approach suggests that lowering soluble Abeta oligomers by inhibiting BACE1 may be beneficial for alleviating cognitive disorders in AD...
  17. pmc Protection against the synaptic targeting and toxicity of Alzheimer's-associated Aβ oligomers by insulin mimetic chiro-inositols
    Jason Pitt
    Department of Neurobiology, Northwestern University, Evanston, Illinois, USA
    FASEB J 27:199-207. 2013
    ..We propose that inositol glycans and DCI, a compound already established as safe for human consumption, have potential as AD therapeutics by protecting CNS synapses against Aβ oligomers through their insulin mimetic activity...
  18. pmc Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss
    Yuesong Gong
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 100:10417-22. 2003
    ..Current results confirm the prediction that soluble oligomeric A beta ligands are intrinsic to AD pathology, and validate their use in new approaches to therapeutic AD drugs and vaccines...
  19. ncbi request reprint Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
    Hai Wei Wang
    Department of Pediatrics, Northwestern University Medical School and Evanston Hospital, Evanston, IL 60201, USA
    Brain Res 924:133-40. 2002
    ....
  20. ncbi request reprint ADDLs & protofibrils--the missing links?
    William L Klein
    Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Institute for Neuroscience, Evanston, IL 60208, USA
    Neurobiol Aging 23:231-5. 2002
  21. ncbi request reprint Per-6-substituted beta-cyclodextrin libraries inhibit formation of beta-amyloid-peptide (A beta)-derived, soluble oligomers
    Jiaxin Yu
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The University of Illinois at Chicago, 60612, USA
    J Mol Neurosci 19:51-5. 2002
    ..These preliminary experiments suggest that derivatized forms of beta-CD can interfere with the oligomerization process of A beta(1-42)...
  22. ncbi request reprint Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein
    Hyeon Jin Kim
    Research Division, Jinis Biopharmaceuticals Co, Chonju, Chonbuk, South Korea
    FASEB J 17:118-20. 2003
    ....
  23. ncbi request reprint Synaptic targeting by Alzheimer's-related amyloid beta oligomers
    Pascale N Lacor
    Neurobiology and Physiology Department, Northwestern University, Evanston, Illinois 60208, USA5
    J Neurosci 24:10191-200. 2004
    ..Results suggest the hypothesis that targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early AD...
  24. doi request reprint Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model
    Chiho Hirata-Fukae
    Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA
    Brain Res 1216:92-103. 2008
    ..These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research...
  25. pmc Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer mice
    Ann C McKee
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    Brain Res 1207:225-36. 2008
    ..These findings provide further support for intraneuronal Abeta as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric Abeta accumulation...
  26. ncbi request reprint Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology
    Salvatore Oddo
    Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4545, USA
    J Biol Chem 281:1599-604. 2006
    ..Therefore, Abeta oligomers may play a role in the induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target...
  27. pmc PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42
    Olivier Boutaud
    Department of Pharmacology, Vanderbilt University, Nashville 37232 6602, Tennessee, USA
    J Neurochem 96:917-23. 2006
    ....
  28. ncbi request reprint Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxicty
    Siva Sundara Kumar Durairajan
    School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
    Neurochem Int 52:741-50. 2008
    ..These results suggest that Sal B has therapeutic potential in the treatment of AD, and warrant its study in animal models...
  29. ncbi request reprint Per-6-substituted-per-6-deoxy beta-cyclodextrins inhibit the formation of beta-amyloid peptide derived soluble oligomers
    Zhiqiang Wang
    J Med Chem 47:3329-33. 2004
    ..In the present work we describe the preparation of per-6-amino-6-deoxy-beta-cyclodextrins, which inhibit ADDLs formation in vitro...
  30. ncbi request reprint Self-assembly of Abeta(1-42) into globular neurotoxins
    Brett A Chromy
    Biodefense Division, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, 7000 East Avenue, L 446, Livermore, California 94551, USA
    Biochemistry 42:12749-60. 2003
    ..The observed neurotoxicity, structure, and stability of synthetic Abeta(1-42) globular assemblies support the hypothesis that Abeta(1-42) oligomers play a role in triggering nerve cell dysfunction and death in Alzheimer's disease...
  31. ncbi request reprint Cyclic AMP enhancers and Abeta oligomerization blockers as potential therapeutic agents in Alzheimer's disease
    Fernanda G De Felice
    Instituto de Bioquimica Medica, Programa de Bioquimica e Biofisica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944 590, Brazil
    Curr Alzheimer Res 4:263-71. 2007
    ..Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed...
  32. ncbi request reprint Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans
    Yanjue Wu
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA
    J Neurosci 26:13102-13. 2006
    ....