ROBERT J VASSAR

Summary

Affiliation: Northwestern University
Country: USA

Publications

  1. doi request reprint ADAM10 prodomain mutations cause late-onset Alzheimer's disease: not just the latest FAD
    Robert Vassar
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, 300 East Superior Street, Tarry 8 713, Chicago, IL 60611 3006, USA Electronic address
    Neuron 80:250-3. 2013
  2. ncbi request reprint Elevated Aβ42 in aged, non-demented individuals with cerebral atherosclerosis
    Katherine R Sadleir
    Northwestern University, The Feinberg School of Medicine, Department of Cell and Molecular Biology, 300 East Superior Street Tarry 8 713, Chicago, IL USA 60611 3006
    Curr Alzheimer Res 10:785-9. 2013
  3. pmc Neuron loss in the 5XFAD mouse model of Alzheimer's disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation
    William A Eimer
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA
    Mol Neurodegener 8:2. 2013
  4. pmc The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb
    Tharinda W Rajapaksha
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Neurodegener 6:88. 2011
  5. pmc The Alzheimer's disease beta-secretase enzyme, BACE1
    Sarah L Cole
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago Avenue, Chicago, IL, USA
    Mol Neurodegener 2:22. 2007
  6. pmc The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential
    Robert Vassar
    Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 29:12787-94. 2009
  7. pmc BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization
    Brian D Hitt
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Neurodegener 5:31. 2010
  8. pmc The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease
    Robert Vassar
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 300 E, Superior, Tarry 8 713, Chicago, IL 60611, USA
    Alzheimers Res Ther 3:20. 2011
  9. pmc The contribution of activated astrocytes to Aβ production: implications for Alzheimer's disease pathogenesis
    Jie Zhao
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Neuroinflammation 8:150. 2011
  10. ncbi request reprint Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's disease
    Robert Vassar
    Department of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611 3006, USA
    Neuron 54:671-3. 2007

Collaborators

Detail Information

Publications27

  1. doi request reprint ADAM10 prodomain mutations cause late-onset Alzheimer's disease: not just the latest FAD
    Robert Vassar
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, 300 East Superior Street, Tarry 8 713, Chicago, IL 60611 3006, USA Electronic address
    Neuron 80:250-3. 2013
    ..These results support both ADAM10 as a therapeutic target and the amyloid hypothesis of Alzheimer's disease...
  2. ncbi request reprint Elevated Aβ42 in aged, non-demented individuals with cerebral atherosclerosis
    Katherine R Sadleir
    Northwestern University, The Feinberg School of Medicine, Department of Cell and Molecular Biology, 300 East Superior Street Tarry 8 713, Chicago, IL USA 60611 3006
    Curr Alzheimer Res 10:785-9. 2013
    ....
  3. pmc Neuron loss in the 5XFAD mouse model of Alzheimer's disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation
    William A Eimer
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA
    Mol Neurodegener 8:2. 2013
    ..5XFAD mice exhibit intraneuronal Aβ42 accumulation at 1.5 months, amyloid deposition at 2 months, and memory deficits by 4 months of age...
  4. pmc The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb
    Tharinda W Rajapaksha
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Neurodegener 6:88. 2011
    ..Here, we used a genetic approach to investigate the function of BACE1 in axon guidance of olfactory sensory neurons (OSNs), a well-studied model of axon targeting in vivo...
  5. pmc The Alzheimer's disease beta-secretase enzyme, BACE1
    Sarah L Cole
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago Avenue, Chicago, IL, USA
    Mol Neurodegener 2:22. 2007
    ....
  6. pmc The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential
    Robert Vassar
    Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 29:12787-94. 2009
    ..The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE...
  7. pmc BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization
    Brian D Hitt
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Neurodegener 5:31. 2010
    ..Examination of BACE1-/- mice can provide insight into this function and also help anticipate consequences of BACE1 inhibition. Here we report a seizure-susceptibility phenotype that we have identified and characterized in BACE1-/- mice...
  8. pmc The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease
    Robert Vassar
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 300 E, Superior, Tarry 8 713, Chicago, IL 60611, USA
    Alzheimers Res Ther 3:20. 2011
    ..We conclude that therapeutic inhibition of BACE1 should be efficacious for AD, although careful titration of the drug dose may be necessary to limit mechanism-based side effects...
  9. pmc The contribution of activated astrocytes to Aβ production: implications for Alzheimer's disease pathogenesis
    Jie Zhao
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Neuroinflammation 8:150. 2011
    ..Here, we explored whether pro-inflammatory cytokines or Aβ42 would increase astrocytic levels of BACE1, APP, and β-secretase processing, implying a feed-forward mechanism of astrocytic Aβ production...
  10. ncbi request reprint Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's disease
    Robert Vassar
    Department of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611 3006, USA
    Neuron 54:671-3. 2007
    ..In this issue of Neuron, Tesco et al. show that during apoptosis caspase-3 cleaves the adaptor protein GGA3, which is required for BACE lysosomal degradation, consequently stabilizing BACE and elevating Abeta generation...
  11. ncbi request reprint The beta-secretase, BACE: a prime drug target for Alzheimer's disease
    R Vassar
    Northwestern University Medical School, Department of Cell and Molecular Biology, Chicago, IL 60611, USA
    J Mol Neurosci 17:157-70. 2001
    ..In addition, I discuss recent studies of BACE1 knockout mice and the BACE1 X-ray structure, and relate implications for BACE1 drug development...
  12. ncbi request reprint Beta-secretase (BACE) as a drug target for Alzheimer's disease
    Robert Vassar
    Northwestern University Medical School, Department of Cell and Molecular Biology, 303 East Chicago Avenue, Chicago, IL 60611, USA
    Adv Drug Deliv Rev 54:1589-602. 2002
    ..Finally, recent studies of BACE1 knockout mice, the BACE1 X-ray structure, and implications for BACE1 drug development will be discussed...
  13. ncbi request reprint BACE1: the beta-secretase enzyme in Alzheimer's disease
    Robert Vassar
    The Feinberg School of Medicine, Northwestern University, Department of Cell and Molecular Biology, Chicago, IL 60611, USA
    J Mol Neurosci 23:105-14. 2004
    ..This review discusses the identification and initial characterization of BACE1 and BACE2, and summarizes recent studies of BACE1 knockout mice that have validated BACE1 as the authentic beta-secretase in vivo...
  14. pmc Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis
    Tracy O'Connor
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Neuron 60:988-1009. 2008
    ..These results strongly suggest that eIF2alpha phosphorylation increases BACE1 levels and causes Abeta overproduction, which could be an early, initiating molecular mechanism in sporadic AD...
  15. pmc Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts
    Kulandaivelu S Vetrivel
    Department of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 284:3793-803. 2009
    ..These results indicate that post-translational S-palmitoylation of BACE1 is not required for APP processing, and that BACE1 can efficiently cleave APP in both raft and non-raft microdomains...
  16. pmc BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice
    Masuo Ohno
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 3008, USA
    Neurobiol Dis 26:134-45. 2007
    ..Our findings provide strong evidence that Abeta ultimately is responsible for neuron death in AD and validate the therapeutic potential of BACE1-inhibiting approaches for the treatment of AD...
  17. ncbi request reprint Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis
    Jie Zhao
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Neurosci 27:3639-49. 2007
    ..We conclude that BACE1 elevation is most likely triggered by the amyloid pathway and may drive a positive-feedback loop in AD...
  18. ncbi request reprint Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesis
    Rodney A Velliquette
    Department of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Neurosci 25:10874-83. 2005
    ..This process may represent one of the earliest pathogenic events in AD...
  19. pmc Beta-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer disease
    Brent L Kelly
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    J Biol Chem 280:31746-53. 2005
    ..These data suggest a mechanism to explain the early cognitive loss without a major decline in synapse number observed in AD and propose a novel therapeutic target for AD intervention...
  20. ncbi request reprint beta-Secretase, APP and Abeta in Alzheimer's disease
    Robert Vassar
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Subcell Biochem 38:79-103. 2005
    ..Here, I review the roles of BACE1, APP, and Abeta in AD and discuss the implications of therapeutic approaches that target BACE1 for the treatment of AD...
  21. ncbi request reprint BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease
    Masuo Ohno
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Neuron 41:27-33. 2004
    ..Our gene-based approach demonstrates that lower Abeta levels are beneficial for AD-associated memory impairments, validating BACE1 as a therapeutic target for AD...
  22. ncbi request reprint Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation
    Holly Oakley
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 26:10129-40. 2006
    ..Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation...
  23. ncbi request reprint Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism
    Sarah L Cole
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Biol Chem 280:18755-70. 2005
    ....
  24. 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...
  25. pmc Linking vascular disorders and Alzheimer's disease: potential involvement of BACE1
    Sarah L Cole
    Northwestern University, The Feinberg School of Medicine, Department of Cell and Molecular Biology, 303 E Chicago Avenue, Chicago, IL 60611, USA
    Neurobiol Aging 30:1535-44. 2009
    ..However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation...
  26. pmc The role of amyloid precursor protein processing by BACE1, the beta-secretase, in Alzheimer disease pathophysiology
    Sarah L Cole
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 283:29621-5. 2008
    ..We address pertinent questions such as putative causes of BACE1 elevation in AD and discuss why, nine years since the identification of BACE1, treatments that address the underlying pathological mechanisms of AD are still lacking...
  27. ncbi request reprint BACE1 structure and function in health and Alzheimer's disease
    Sarah L Cole
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago Avenue, Chicago, IL, USA
    Curr Alzheimer Res 5:100-20. 2008
    ....

Research Grants12

  1. BACE1 as a Therapeutic Target for Alzheimer's Disease
    ROBERT J VASSAR; Fiscal Year: 2010
    ..In addition, we will investigate the effects of BACE1 inhibition on the brain in order to understand potential side-effects of BACE1 inhibitor drugs. ..
  2. BACE1 as a Therapeutic Target for Alzheimer's Disease
    Robert Vassar; Fiscal Year: 2007
    ..These Aims will test our overall hypothesis that BACE1 is a valid drug target, and we expect our results will strengthen the conceptual foundation for the development of BACE1 and gamma-secretase inhibitors for AD. ..
  3. Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's Disease
    Robert Vassar; Fiscal Year: 2007
    ..Inhibition of BACE1 elevation should reduce A¿ without directly blocking BACE1 and thus may be efficacious without side-effects for Alzheimer's disease. ..
  4. Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's Disease
    ROBERT J VASSAR; Fiscal Year: 2010
    ..Inhibition of BACE1 elevation should reduce A without directly blocking BACE1 and thus may be efficacious without side-effects for Alzheimer's disease. ..