David Holtzman

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. pmc Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
    JASON D ULRICH
    Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    Mol Neurodegener 9:20. 2014
  2. pmc Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis
    Rebecca Craig-Schapiro
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS ONE 6:e18850. 2011
  3. pmc Neuronal activity regulates the regional vulnerability to amyloid-β deposition
    Adam W Bero
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Neurosci 14:750-6. 2011
  4. pmc Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
    Jungsu Kim
    Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    J Exp Med 209:2149-56. 2012
  5. pmc Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects
    Saori Hata
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Mol Neurodegener 7:16. 2012
  6. pmc In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
    JASON D ULRICH
    Department of Neurology, Saint Louis, MO, USA
    Mol Neurodegener 8:13. 2013
  7. pmc Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease
    David M Holtzman
    Department of Neurology, Alzheimer s Disease Research Center, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cold Spring Harb Perspect Med 2:a006312. 2012
  8. pmc Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling
    Jacob M Basak
    Department of Neurology, Saint Louis, Missouri 63110, USA
    Mol Neurodegener 7:14. 2012
  9. pmc CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease
    R Tarawneh
    Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
    Neurology 78:709-19. 2012
  10. pmc CSF biomarkers for Alzheimer's disease: current utility and potential future use
    David M Holtzman
    Department of Neurology, Developmental Biology, Knight Alzheimer s Disease Research Center, and the Hope Center for Neurological Disorders, Washington University, St Louis, MO 63110, USA
    Neurobiol Aging 32:S4-9. 2011

Research Grants

  1. Effect of apoE on CNS neurons: Role of LRP
    David Holtzman; Fiscal Year: 2007
  2. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2003
  3. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2002
  4. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2002
  5. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2001
  6. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2000
  7. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 1999
  8. NERVOUS SYSTEM DEVELOPMENT AND INJURY
    David Holtzman; Fiscal Year: 2007
  9. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2003
  10. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2001

Detail Information

Publications99

  1. pmc Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
    JASON D ULRICH
    Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    Mol Neurodegener 9:20. 2014
    ....
  2. pmc Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis
    Rebecca Craig-Schapiro
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS ONE 6:e18850. 2011
    ..We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181)...
  3. pmc Neuronal activity regulates the regional vulnerability to amyloid-β deposition
    Adam W Bero
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Neurosci 14:750-6. 2011
    ..Long-term unilateral vibrissal deprivation decreased amyloid plaque formation and growth. Our results suggest a mechanism to account for the vulnerability of specific brain regions to Aβ deposition in Alzheimer's disease...
  4. pmc Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
    Jungsu Kim
    Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    J Exp Med 209:2149-56. 2012
    ..Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases...
  5. pmc Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects
    Saori Hata
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Mol Neurodegener 7:16. 2012
    ..Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD)...
  6. pmc In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
    JASON D ULRICH
    Department of Neurology, Saint Louis, MO, USA
    Mol Neurodegener 8:13. 2013
    ..We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes...
  7. pmc Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease
    David M Holtzman
    Department of Neurology, Alzheimer s Disease Research Center, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cold Spring Harb Perspect Med 2:a006312. 2012
    ..Understanding the normal and disease-related biology connecting apoE, apoE receptors, and AD is likely to provide novel insights into AD pathogenesis and treatment...
  8. pmc Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling
    Jacob M Basak
    Department of Neurology, Saint Louis, Missouri 63110, USA
    Mol Neurodegener 7:14. 2012
    ..We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain...
  9. pmc CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease
    R Tarawneh
    Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA
    Neurology 78:709-19. 2012
    ..Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early AD...
  10. pmc CSF biomarkers for Alzheimer's disease: current utility and potential future use
    David M Holtzman
    Department of Neurology, Developmental Biology, Knight Alzheimer s Disease Research Center, and the Hope Center for Neurological Disorders, Washington University, St Louis, MO 63110, USA
    Neurobiol Aging 32:S4-9. 2011
    ..The markers are also useful in predicting conversion from cognitive normalcy to very mild dementia. This field is briefly reviewed and recommendations for future studies in this area are provided...
  11. doi request reprint Mapping the road forward in Alzheimer's disease
    David M Holtzman
    Department of Neurology, Washington University, St Louis, MO 63110, USA
    Sci Transl Med 3:114ps48. 2011
    ..We hope these recommendations will boost research progress in AD and increase the likelihood of developing effective therapies in the near future...
  12. pmc Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo
    John W Steele
    Departments of Neurology, Psychiatry and Alzheimer s Disease Research Center, Mount Sinai School of Medicine, New York, NY, 10029, USA
    Mol Neurodegener 4:51. 2009
    ..In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Abeta using in vitro and in vivo experimental systems...
  13. pmc Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD
    Parastoo Momeni
    Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD, USA
    BMC Neurol 6:44. 2006
    ..A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p...
  14. ncbi request reprint Amyloid-beta binding molecule: potential role in the pathogenesis and treatment of Alzheimer disease
    David M Holtzman
    Department of Neurology, Molecular Biology of Pharmacology, Washington University Alzheimer s Research Center, St Louis, Missouri, USA
    Alzheimer Dis Assoc Disord 17:S66-8. 2003
  15. pmc Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease
    D M Holtzman
    Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 103:R15-R21. 1999
    ..The results may have important implications for understanding mechanisms underlying the link between apo E and AD...
  16. ncbi request reprint Role of apoe/Abeta interactions in the pathogenesis of Alzheimer's disease and cerebral amyloid angiopathy
    D M Holtzman
    Alzheimer s Disease Research Center, Department of Neurology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Mol Neurosci 17:147-55. 2001
    ..These studies also suggest a role for human apoE in Abeta clearance in vivo...
  17. pmc A surrogate marker for Abeta42 production in the CNS
    David M Holtzman
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, and the Alzheimer s Disease Research Center, Washington University, St Louis, MO 63110, USA
    EMBO Mol Med 1:195-7. 2009
    ..There is overwhelming genetic and biochemical evidence that the aggregation and buildup of the amyloid-beta (Abeta) peptide plays a critical role in AD pathogenesis...
  18. ncbi request reprint Potential role of endogenous and exogenous amyloid-beta binding molecules in the pathogenesis, diagnosis, and treatment of Alzheimer disease
    David M Holtzman
    Washington University School of Medicine Dept of Neurology, St Louis 63110, USA
    Alzheimer Dis Assoc Disord 17:151-3. 2003
  19. ncbi request reprint In vivo effects of ApoE and clusterin on amyloid-beta metabolism and neuropathology
    David M Holtzman
    Center for the Study of Nervous System Injury, Alzheimer s Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Mol Neurosci 23:247-54. 2004
    ....
  20. pmc Alzheimer's disease: the challenge of the second century
    David M Holtzman
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Sci Transl Med 3:77sr1. 2011
    ..Current information suggests that if the disease is detected before the onset of overt symptoms, it is possible that treatments based on knowledge of underlying pathogenesis can and will be effective...
  21. ncbi request reprint ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo
    Ronald B DeMattos
    Neuroscience Discovery Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA
    Neuron 41:193-202. 2004
    ..These findings demonstrate additive effects of apoE and clusterin on influencing Abeta deposition and that apoE plays an important role in regulating extracellular CNS Abeta metabolism independent of Abeta synthesis...
  22. ncbi request reprint Expression of neuronal-NOS in developing basal forebrain cholinergic neurons: regulation by NGF
    D M Holtzman
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Neurochem Res 21:861-8. 1996
    ..Through enhancing neuronal-NOS synthesis, endogenous NGF is likely to regulate NO functions in vivo...
  23. ncbi request reprint Abeta immunization and anti-Abeta antibodies: potential therapies for the prevention and treatment of Alzheimer's disease
    David M Holtzman
    Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, MO 63110, USA
    Adv Drug Deliv Rev 54:1603-13. 2002
    ..Abeta-related immune therapies in humans are an exciting new area of AD research. Understanding their detailed mechanism(s) of action and their potential usefulness awaits the results of future animal and human studies...
  24. ncbi request reprint In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life
    John R Cirrito
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:8844-53. 2003
    ..This now measurable in vivo pool is a likely target for new diagnostic and therapeutic strategies...
  25. ncbi request reprint Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model
    John D Fryer
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 25:2803-10. 2005
    ....
  26. ncbi request reprint ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE
    Suzanne E Wahrle
    Program in Neurosciences, Washington University, St Louis, Missouri 63110, USA
    J Biol Chem 279:40987-93. 2004
    ..Since apoE isoforms and levels strongly influence Alzheimer's disease pathology and risk, these data suggest that ABCA1 may be a novel therapeutic target...
  27. pmc Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice
    Ping Yan
    Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 29:10706-14. 2009
    ..Together, these findings indicate that individual amyloid plaque growth in vivo occurs over a period of weeks and may be influenced by interstitial Abeta concentration as well as reactive gliosis...
  28. ncbi request reprint Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease
    Richard E Hartman
    Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 22:10083-7. 2002
    ..These data support the hypothesis that APOE4 influences the neurodegenerative cascade after TBI via an effect on Abeta...
  29. pmc Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease
    Ronald B DeMattos
    Center for the Study of Nervous System Injury, Alzheimer s Disease Research Center, and Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 99:10843-8. 2002
    ..These findings demonstrate that clusterin markedly influences Abeta structure and neuritic toxicity in vivo and is likely to play an important role in Alzheimer's disease pathogenesis...
  30. ncbi request reprint Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice
    John D Fryer
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:7889-96. 2003
    ..These findings demonstrate that murine apoE markedly promotes the formation of CAA and associated vessel damage and that the effect of apoE combined with the level of Abeta40 or the ratio of Abeta 40:42 facilitates this process...
  31. ncbi request reprint Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease
    Suzanne E Wahrle
    Program in Neurosciences, Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:43236-42. 2005
    ..Together, these data suggest that despite substantially lower apoE levels, poorly lipidated apoE produced in the absence of ABCA1 is strongly amyloidogenic in vivo...
  32. ncbi request reprint Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo
    John R Cirrito
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Neuron 48:913-22. 2005
    ..The findings also have important implications for treatment development...
  33. pmc Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report
    Nigel J Cairns
    Alzheimer s Disease Research Center, Washington University, St Louis, Missouri 63108, USA
    Arch Neurol 66:1557-62. 2009
    ....
  34. pmc Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle
    Jae Eun Kang
    Department of Neurology, Washington University, St Louis, MO 63110, USA
    Science 326:1005-7. 2009
    ..Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease...
  35. ncbi request reprint Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice
    Celina V Zerbinatti
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:36180-6. 2006
    ..Our results support the hypothesis that LRP binds and endocytoses Abeta42 both directly and via apoE but that endocytosed Abeta42 is not completely degraded and accumulates in intraneuronal lysosomes...
  36. pmc Rapid microglial response around amyloid pathology after systemic anti-Abeta antibody administration in PDAPP mice
    Jessica Koenigsknecht-Talboo
    Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 28:14156-64. 2008
    ..These findings demonstrate that some effects of antibodies that recognize aggregated Abeta are rapid, involve microglia, and provide insight into the mechanism of action of a specific passive immunotherapy for AD...
  37. pmc Biomarkers of Alzheimer's disease
    Rebecca Craig-Schapiro
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurobiol Dis 35:128-40. 2009
    ..More recently, better reagent availability and novel methods of assessment have further spurred the search for biomarkers of AD. This review will discuss promising fluid and imaging markers to date...
  38. pmc Exercise and Alzheimer's disease biomarkers in cognitively normal older adults
    Kelvin Y Liang
    From the Program in Neuroscience, Division of Biology and Biomedical Sciences, Washington University, St Louis, MO 63130, USA
    Ann Neurol 68:311-8. 2010
    ..The objective of this study was to elucidate the association between exercise and AD pathology in humans using Pittsburgh compound-B (PIB), amyloid-beta (Abeta)(42), tau, and phosphorylated tau (ptau)(181) biomarkers...
  39. pmc A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice
    Marcin Sadowski
    Department of Neurology, New York University School of Medicine, New York, New York, USA
    Am J Pathol 165:937-48. 2004
    ..Our experiments demonstrate that compounds blocking the interaction between Abeta and its pathological chaperones may be beneficial for treatment of beta-amyloid deposition in AD...
  40. ncbi request reprint The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice
    John D Fryer
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:25754-9. 2005
    ....
  41. pmc Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease
    Hua Cheng
    Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurobiol Aging 31:1188-96. 2010
    ..Collectively, through different animal models of AD, this study provides evidence for an identified biochemical mechanism that may be responsible for the sulfatide depletion at the earliest stages of AD...
  42. pmc Role of family history for Alzheimer biomarker abnormalities in the adult children study
    Chengjie Xiong
    Charles F and Joanne Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA
    Arch Neurol 68:1313-9. 2011
    ..To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities...
  43. pmc Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Harvard Institutes of Medicine, Room 730, Boston, MA 02115, USA
    Am J Pathol 171:241-51. 2007
    ....
  44. pmc Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
    Suzanne E Wahrle
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 118:671-82. 2008
    ..These data support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD...
  45. ncbi request reprint Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease
    Ronald B DeMattos
    Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 81:229-36. 2002
    ..These findings suggest that there is a dynamic equilibrium between CNS and plasma Abeta, and that plaques create a new equilibrium because soluble CNS Abeta not only enters the plasma but also deposits onto amyloid plaques in the CNS...
  46. ncbi request reprint The bad seed in Alzheimer's disease
    John D Fryer
    Department of Neurology and Molecular Biology and Pharmacology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 47:167-8. 2005
    ..have produced mice that overexpress only Abeta40 or Abeta42 and prove that Abeta42 is critical for the formation of amyloid deposits in vivo...
  47. pmc Critical issues for successful immunotherapy in Alzheimer's disease: development of biomarkers and methods for early detection and intervention
    Rawan Tarawneh
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    CNS Neurol Disord Drug Targets 8:144-59. 2009
    ..Current work with AD biomarkers suggests that such individuals can now be identified and it seems likely that targeting this population with immunization strategies targeting Abeta would offer the best chance of success...
  48. ncbi request reprint Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging
    Shu Wei Sun
    Department of Radiology, Washington University School of Medicine, St Louis, MO 63130, USA
    Exp Neurol 191:77-85. 2005
    ..This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues...
  49. ncbi request reprint Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta
    Margaret M Racke
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    J Neurosci 25:629-36. 2005
    ..These results may have important implications for future immune-based therapeutic strategies for Alzheimer's disease...
  50. pmc Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance
    Jungsu Kim
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 64:632-44. 2009
    ..Plaque-associated neuroinflammatory responses were attenuated in LDLR transgenic mice. These findings suggest that increasing LDLR levels may represent a novel AD treatment strategy...
  51. pmc Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: contribution of soluble and insoluble amyloid-beta peptide, partial restoration via gamma-secretase inhibition
    Byung Hee Han
    Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 28:13542-50. 2008
    ....
  52. pmc Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease
    Melanie Meyer-Luehmann
    Alzheimer s Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 451:720-4. 2008
    ..Progressive neuritic changes ensue, leading to increasingly dysmorphic neurites over the next days to weeks. These data establish plaques as a critical mediator of neuritic pathology...
  53. pmc Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex
    Ling Hui Zeng
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurobiol Dis 28:184-96. 2007
    ..These results suggest that abnormal glutamate homeostasis predisposes to excitotoxic cell death, impaired synaptic plasticity and learning deficits in Tsc1 GFAP CKO mice...
  54. ncbi request reprint Quantitative analysis of amyloid-beta peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry
    Valentina Gelfanova
    Integrative Biology Division, Lilly Research Laboratories, Greenfield, IN 46140, USA
    Brief Funct Genomic Proteomic 6:149-58. 2007
    ..Application of the MALDI-Tof assay to CSF obtained from healthy volunteers and Alzheimer's disease patients indicated statistically significant 43% lower levels of Abeta(1-42) in the AD group (P = 0.0025)...
  55. ncbi request reprint Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model
    Jean Cosme Dodart
    Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
    Nat Neurosci 5:452-7. 2002
    ....
  56. ncbi request reprint Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism
    Ke Jie Yin
    Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 26:10939-48. 2006
    ..These results suggest that MMP-2 and -9 may contribute to extracellular brain Abeta clearance by promoting Abeta catabolism...
  57. ncbi request reprint Amyloid-beta immunotherapies in mice and men
    Robert P Brendza
    Department of Neurology, Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA wustl edu
    Alzheimer Dis Assoc Disord 20:118-23. 2006
    ....
  58. ncbi request reprint Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease
    Ronald B DeMattos
    Center for the Study of Nervous System Injury, Alzheimer s Disease Research Center, Department of Neurology, Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St Louis, MO 63110, USA
    Science 295:2264-7. 2002
    ..This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD...
  59. pmc P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model
    John R Cirrito
    Department of Neurology, Washington University Medical School, St Louis, Missouri 63110, USA
    J Clin Invest 115:3285-90. 2005
    ..These data establish a direct link between Pgp and Abeta metabolism in vivo and suggest that Pgp activity at the BBB could affect risk for developing AD as well as provide a novel diagnostic and therapeutic target...
  60. ncbi request reprint Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-beta
    Masayuki Morikawa
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63130, USA
    Neurobiol Dis 19:66-76. 2005
    ..These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS...
  61. ncbi request reprint Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans
    Anne M Fagan
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 59:512-9. 2006
    ..This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and CSF. We investigated this hypothesis...
  62. pmc Morris water maze search strategy analysis in PDAPP mice before and after experimental traumatic brain injury
    David L Brody
    Department of Neurology, Washington University, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    Exp Neurol 197:330-40. 2006
    ..Human TBI patients may have analogous poor use of problem solving strategies...
  63. pmc Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease
    Anne M Fagan
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    EMBO Mol Med 1:371-80. 2009
    ..These findings have important implications for preclinical AD diagnosis and treatment...
  64. pmc Cerebrospinal fluid biomarkers of Alzheimer's disease
    Anne M Fagan
    Department of Neurology, Hope Center for Neuological Disorder, Washington University, School of Medicine, St Louis, MO 63110, USA
    Biomark Med 4:51-63. 2010
    ..This article summarizes the most promising cerebrospinal fluid biomarkers, highlights novel applications and current challenges, and provides a prediction on how the field may evolve in 5-10 years...
  65. pmc Relationship of dementia screening tests with biomarkers of Alzheimer's disease
    James E Galvin
    Alzheimer s Disease Research Centre, Washington University, St Louis, MO 63108, USA
    Brain 133:3290-300. 2010
    ....
  66. pmc Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease
    Richard J Perrin
    Division of Neuropathology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS ONE 6:e16032. 2011
    ..To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome...
  67. ncbi request reprint Differential metabolism of ApoE isoforms in plasma and CSF
    Suzanne E Wahrle
    Program in Neurosciences, Washington University School of Medicine, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    Exp Neurol 183:4-6. 2003
  68. ncbi request reprint Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia
    Xianlin Han
    Division of Bioorganic Chemistry and Molecular Pharmacology, and the Departments of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 54:115-9. 2003
    ..The cerebrospinal fluid ST to phosphatidylinositol ratio may be a very useful biomarker for the earliest clinical stage of Alzheimer's disease...
  69. ncbi request reprint Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease
    Anne M Fagan
    Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Neurobiol Dis 9:305-18. 2002
    ....
  70. pmc Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo
    Randall J Bateman
    Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St Louis, Missouri 63110, USA
    Nat Med 12:856-61. 2006
    ....
  71. pmc Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly
    Anne M Fagan
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 65:176-83. 2009
    ..The objective of this study was to determine whether cerebrospinal fluid (CSF) biomarkers for AD suggest the presence of brain damage in the preclinical stage of AD...
  72. ncbi request reprint Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker
    Randall J Bateman
    Dept of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurology 68:666-9. 2007
    ..To investigate the stability and time course of human CSF amyloid-beta (Abeta) levels over hours...
  73. ncbi request reprint Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults
    Anne M Fagan
    Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    Arch Neurol 64:343-9. 2007
    ....
  74. ncbi request reprint Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation
    John S K Kauwe
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
    Ann Neurol 61:446-53. 2007
    ..Mutations in presenilin 1 (PSEN1) are known to cause AD and change Abeta levels. In this study, we have investigated DNA sequence variation in the presenilin (PSEN1) gene using CSF Abeta levels as an endophenotype for AD...
  75. pmc Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury
    David L Brody
    Department of Neurology, Hope Center for Neurological Disorders, Washington University, St Louis, Missouri, USA
    J Neurotrauma 24:657-73. 2007
    ..0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice...
  76. pmc Amyloid-beta dynamics correlate with neurological status in the injured human brain
    David L Brody
    Department of Neurology, Washington University, St Louis, MO 63110, USA
    Science 321:1221-4. 2008
    ..Such dynamics fit well with the hypothesis that neuronal activity regulates extracellular Abeta concentration...
  77. pmc Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity
    Jae Eun Kang
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 104:10673-8. 2007
    ..Thus, behavioral stressors can rapidly increase ISF Abeta through neuronal activity in a CRF-dependent manner, and the results suggest a mechanism by which behavioral stress may affect Alzheimer's disease pathogenesis...
  78. pmc Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta
    John S K Kauwe
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
    Neurogenetics 10:13-7. 2009
    ....
  79. pmc Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia
    John G Csernansky
    Alzheimer s Disease Research Center and the Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
    Am J Psychiatry 163:2164-9. 2006
    ....
  80. pmc Active and passive immunotherapy for neurodegenerative disorders
    David L Brody
    Department of Neurology, Developmental Biology, Alzheimer s Disease Research Center, and Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Annu Rev Neurosci 31:175-93. 2008
    ....
  81. pmc Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury
    Christine L Mac Donald
    Department of Biomedical Engineering, Washington University, St Louis, Missouri 63130, USA
    J Neurosci 27:11869-76. 2007
    ..Remarkably, DTI changes strongly predicted the approximate time since trauma. These results provide an important validation of DTI for pericontusional TAI and suggest novel clinical and forensic applications...
  82. pmc The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-ε4 carriers
    Bruno A Benítez
    Department of Psychiatry, School of Medicine, Washington University, St Louis, Missouri, United States of America
    PLoS Genet 9:e1003685. 2013
    ..We demonstrate that the effect of PSEN1, p.E318G on AD susceptibility is largely dependent on an interaction with APOE-ε4 and mediated by an increased burden of Aβ deposition...
  83. ncbi request reprint Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice
    Cynthia A Lemere
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Dis 14:10-8. 2003
    ..Most of the Abeta in the serum of the immunized mice was bound to antibodies. We conclude that following active immunization, anti-Abeta antibodies sequester serum Abeta and may increase central nervous system to serum Abeta clearance...
  84. ncbi request reprint Matrix metalloproteinase-9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy
    Jin Moo Lee
    Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 S Euclid Avenue, Campus Box 8111, St Louis, MO, USA
    Ann Neurol 54:379-82. 2003
    ..These results suggest that increased vascular MMP-9 expression, stimulated by Abeta, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage in patients with CAA...
  85. ncbi request reprint Abeta conformational change is central to Alzheimer's disease
    David M Holtzman
    Department of Neurology, Center for the Study of Nervous System Injury, Alzheimer s Disease Research Center, Washington University School of Medicine, 660 S Euclid Avenue, Box 8111, St Louis, MO 63110, USA
    Neurobiol Aging 23:1085-8. 2002
  86. ncbi request reprint Expression of human apolipoprotein E downregulates amyloid precursor protein-induced ischemic susceptibility
    Milla Koistinaho
    A I Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
    Stroke 33:1905-10. 2002
    ....
  87. ncbi request reprint Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease
    Richard E Hartman
    Department of Psychology, Loma Linda University, Loma Linda, CA 92354, USA
    Neurobiol Dis 24:506-15. 2006
    ..These results suggest that further studies to validate and determine the mechanism of these effects, as well as whether substances in PJ may be useful in AD, should be considered...
  88. ncbi request reprint Alzheimer's Abeta vaccination of rhesus monkeys (Macaca mulatta)
    Sam Gandy
    Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Mech Ageing Dev 125:149-51. 2004
    ..These data support the use of non-human primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimer's Abeta...
  89. ncbi request reprint Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ
    Ping Yan
    Department of Neurology and the Hope Center for Neurological Disorders, Division of Endocrinology, Diabetes, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:24566-74. 2006
    ..These findings suggest that MMP-9 can degrade fAbeta and may contribute to ongoing clearance of plaques from amyloid-laden brains...
  90. ncbi request reprint IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor
    Rashid Deane
    Division of Neurovascular Biology, Department of Neurosurgery, Arthur Kornberg Medical Research Building, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurosci 25:11495-503. 2005
    ..Our data suggest that the FcRn pathway at the BBB plays a crucial role in IgG-assisted Abeta removal from the aging brain...
  91. doi request reprint Alzheimer's disease: Moving towards a vaccine
    David M Holtzman
    Nature 454:418-20. 2008
  92. pmc ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease-like cerebral amyloidosis
    Anne M Fagan
    Department of Neurology and Center for the Study of Nervous System Injury, Alzheimer s Disease Research Center, Washington University School of Medicine, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    Am J Pathol 165:1413-22. 2004
    ..These and other data suggest that it is perhaps the level of brain apolipoprotein E, not cholesterol per se, that plays a primary role in brain Abeta metabolism...
  93. pmc ApoE promotes the proteolytic degradation of Abeta
    Qingguang Jiang
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Neuron 58:681-93. 2008
    ..GW3965 treatment also reversed contextual memory deficits. These data demonstrate a mechanism through which ApoE facilitates the clearance of Abeta from the brain and suggest that LXR agonists may represent a novel therapy for AD...
  94. pmc Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo
    John R Cirrito
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 58:42-51. 2008
    ..These findings have implications for AD pathogenesis and may provide insights into therapeutic intervention...
  95. ncbi request reprint Aging, gender and APOE isotype modulate metabolism of Alzheimer's Abeta peptides and F-isoprostanes in the absence of detectable amyloid deposits
    Jun Yao
    Department of Psychiatry, New York University, The Nathan S Kline Institute for Psychiatric Research, Orangeburg, New York, USA
    J Neurochem 90:1011-8. 2004
    ....
  96. ncbi request reprint Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition
    Sheng Kwei Song
    Department of Chemistry, Washington University, St Louis, MO 63130, USA
    Neurobiol Dis 15:640-7. 2004
    ..Our results suggest that as amyloid beta (Abeta) deposition and levels increase over time in PDAPP mice, these changes lead to primary or secondary white matter injury that can be detected by DTI...
  97. ncbi request reprint Novel role for apolipoprotein E in the central nervous system. Modulation of sulfatide content
    Xianlin Han
    Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 278:8043-51. 2003
    ..This novel role for apoE in the CNS may provide new insights into the connection of apoE with Alzheimer's disease and poor recovery after brain injury...
  98. ncbi request reprint Effect of different anti-Abeta antibodies on Abeta fibrillogenesis as assessed by atomic force microscopy
    Justin Legleiter
    Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA
    J Mol Biol 335:997-1006. 2004
    ....

Research Grants16

  1. Effect of apoE on CNS neurons: Role of LRP
    David Holtzman; Fiscal Year: 2007
    ..Aim 4: To determine the role of the cholesterol efflux pump, ABCA 1, in modulating the levels and metabolism of apoE, cholesterol, phospholipid, and Abeta in the brain. ..
  2. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2003
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  3. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2002
    ..This will determine how anti-Abeta antibodies influence CNS/plasma Abeta transport exchanges. ..
  4. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2002
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  5. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2001
    ..This will determine how anti-Abeta antibodies influence CNS/plasma Abeta transport exchanges. ..
  6. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2000
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  7. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 1999
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  8. NERVOUS SYSTEM DEVELOPMENT AND INJURY
    David Holtzman; Fiscal Year: 2007
    ....
  9. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2003
    ..This will determine how anti-Abeta antibodies influence CNS/plasma Abeta transport exchanges. ..
  10. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2001
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..