David M Holtzman

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. 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
  2. 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
  3. 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
  4. pmc Neuronal activity regulates extracellular tau in vivo
    Kaoru Yamada
    Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110
    J Exp Med 211:387-93. 2014
  5. 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
  6. pmc Cerebrospinal fluid biomarkers, education, brain volume, and future cognition
    Catherine M Roe
    Knight Alzheimer s Disease Research Center, St Louis, MO, USA
    Arch Neurol 68:1145-51. 2011
  7. pmc YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease
    Rebecca Craig-Schapiro
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Biol Psychiatry 68:903-12. 2010
  8. pmc Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease
    John C Morris
    Alzheimer s Disease Research Center, St Louis, Missouri 63108, USA
    Arch Neurol 66:1469-75. 2009
  9. 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
  10. 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

Detail Information

Publications119 found, 100 shown here

  1. 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
  2. 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...
  3. 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...
  4. pmc Neuronal activity regulates extracellular tau in vivo
    Kaoru Yamada
    Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110
    J Exp Med 211:387-93. 2014
    ..The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself...
  5. 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...
  6. pmc Cerebrospinal fluid biomarkers, education, brain volume, and future cognition
    Catherine M Roe
    Knight Alzheimer s Disease Research Center, St Louis, MO, USA
    Arch Neurol 68:1145-51. 2011
    ..Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size...
  7. pmc YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease
    Rebecca Craig-Schapiro
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Biol Psychiatry 68:903-12. 2010
    ..Therefore, biomarkers that detect AD pathology in its early stages and predict dementia onset and progression will be invaluable for patient care and efficient clinical trial design...
  8. pmc Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease
    John C Morris
    Alzheimer s Disease Research Center, St Louis, Missouri 63108, USA
    Arch Neurol 66:1469-75. 2009
    ..To determine whether preclinical Alzheimer disease (AD), as detected by the amyloid-imaging agent Pittsburgh Compound B (PiB) in cognitively normal older adults, is associated with risk of symptomatic AD...
  9. 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
    ....
  10. 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...
  11. 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...
  12. pmc Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration
    Magdalena A Kuszczyk
    Department of Neurology, New York University School of Medicine, New York, NY 10016, USA
    Am J Pathol 182:1750-68. 2013
    ..Data from our co-culture and in vivo experiments indicate an essential role of ApoE in the mechanism of intraneuronal Aβ accumulation and provide evidence that ApoE/Aβ binding antagonists can effectively prevent this process...
  13. 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...
  14. pmc Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition
    Denise Head
    Department of Psychology, Washington University, St Louis, MO 63130, USA
    Arch Neurol 69:636-43. 2012
    ..The primary objective here was to examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults...
  15. pmc Toward a multifactorial model of Alzheimer disease
    Martha Storandt
    Department of Psychology, Washington University, St Louis, Missouri, USA
    Neurobiol Aging 33:2262-71. 2012
    ..The lack of correlation between these 2 processes and brain volume in the regions most often affected in AD suggests the operation of a third process related to brain atrophy...
  16. pmc APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging
    John C Morris
    Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63108, USA
    Ann Neurol 67:122-31. 2010
    ..To examine interactions of apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging...
  17. 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...
  18. pmc ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions
    Philip B Verghese
    Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 110:E1807-16. 2013
    ..These results provide an alternative frame work for the mechanistic explanations on how apoE isoforms influence the risk of AD pathogenesis...
  19. 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...
  20. pmc Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease
    William T Hu
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
    Neurology 79:897-905. 2012
    ..Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI)...
  21. 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...
  22. pmc SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease
    Carlos Cruchaga
    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS Genet 6:e1001101. 2010
    ..Finally, we believe genome-wide association studies of CSF tau/ptau(181) levels should identify novel genetic variants which will likely influence rate of progression of AD...
  23. pmc Human apoE isoforms differentially regulate brain amyloid-β peptide clearance
    Joseph M Castellano
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Sci Transl Med 3:89ra57. 2011
    ..Our results suggest that APOE alleles contribute to AD risk by differentially regulating clearance of Aβ from the brain, suggesting that Aβ clearance pathways may be useful therapeutic targets for AD prevention...
  24. 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...
  25. pmc Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type
    Barbara J Snider
    Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S Euclid, St Louis, MO 63110, USA
    Arch Neurol 66:638-45. 2009
    ..Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease...
  26. pmc CSF biomarkers of Alzheimer disease: "noncognitive" outcomes
    Catherine M Roe
    From the Knight Alzheimer s Disease Research Center C M R, A M F, E A G, D M H, J C M, Department of Neurology C M R, A M F, D M H, J C M, Hope Center for Neurological Disorders A M F, D M H, Departments of Pathology and Immunology J C M, Physical Therapy J C M, and Occupational Therapy J C M, and Division of Biostatistics E A G, Washington University School of Medicine, St Louis, MO
    Neurology 81:2028-31. 2013
    ....
  27. pmc Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease
    Tammie L S Benzinger
    Departments of Radiology, Biostatistics, Neurology, Pathology and Immunology, and Psychiatry, Washington University School of Medicine, St Louis, MO, 63110
    Proc Natl Acad Sci U S A 110:E4502-9. 2013
    ..Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease. ..
  28. pmc Bcl-x pre-mRNA splicing regulates brain injury after neonatal hypoxia-ischemia
    Qingli Xiao
    Hope Center for Neurological Disorders and Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 32:13587-96. 2012
    ..These results suggest that alternative pre-mRNA splicing may be an important regulatory mechanism for cell death after acute neurological injury and may potentially provide novel targets for intervention...
  29. pmc Cortical binding of pittsburgh compound B, an endophenotype for genetic studies of Alzheimer's disease
    Anthony L Hinrichs
    Department of Psychiatry, Washington University School of Medicine, St Louis, Misouri, USA
    Biol Psychiatry 67:581-3. 2010
    ..Imaging of Abeta deposition in the human brain using Pittsburgh Compound B (PIB) offers the possibility of using cortical PIB binding as a quantitative endophenotype for genetic studies of late-onset Alzheimer's disease (LOAD)...
  30. 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...
  31. 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...
  32. pmc Clinical and biomarker changes in dominantly inherited Alzheimer's disease
    Randall J Bateman
    Washington University School of Medicine, Department of Neurology, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    N Engl J Med 367:795-804. 2012
    ..Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease...
  33. 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...
  34. pmc Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later
    Catherine M Roe
    Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA
    Neurology 80:1784-91. 2013
    ..5 years...
  35. 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...
  36. 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
    ....
  37. pmc Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
    Carlos Cruchaga
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
    Hum Mol Genet 21:4558-71. 2012
    ..Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism (P = 4.49 × 10(-9))...
  38. pmc Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of Aβ uptake and degradation by astrocytes
    Jacob M Basak
    Department of Neurology, Hope Center for Neurological Disorders, Charles F and Joanne Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 287:13959-71. 2012
    ..Therefore, these results identify LDLR as a receptor that mediates Aβ uptake and clearance by astrocytes, and provide evidence that increasing glial LDLR levels may promote Aβ degradation within the brain...
  39. 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...
  40. pmc Quantitative label-free proteomics for discovery of biomarkers in cerebrospinal fluid: assessment of technical and inter-individual variation
    Richard J Perrin
    Division of Neuropathology, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS ONE 8:e64314. 2013
    ....
  41. 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...
  42. pmc Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology
    Anne M Fagan
    Knight Alzheimer s Disease Research Center, St Louis, Missouri, USA
    Arch Neurol 68:1137-44. 2011
    ..Cerebrospinal fluid (CSF) biomarkers of Alzheimer disease (AD) are currently being considered for inclusion in revised diagnostic criteria for research and/or clinical purposes to increase the certainty of antemortem diagnosis...
  43. 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
    ....
  44. pmc Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-β amyloidosis
    Jungsu Kim
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 31:18007-12. 2011
    ....
  45. 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...
  46. pmc Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease
    Carla M Yuede
    Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 South Euclid Ave, St Louis, MO 63110, USA
    Neurobiol Dis 35:426-32. 2009
    ..The results indicate that voluntary exercise may be superior to forced exercise for reducing certain aspects of AD-like deficits - i.e., plaque deposition and memory impairment, in a mouse model of AD...
  47. 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...
  48. ncbi request reprint Treatment with an amyloid-beta antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer's disease
    Richard E Hartman
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 25:6213-20. 2005
    ....
  49. pmc The utility of intraindividual variability in selective attention tasks as an early marker for Alzheimer's disease
    Janet M Duchek
    Department of Psychology, Washington University in St Louis, St Louis, MO 63130, USA
    Neuropsychology 23:746-58. 2009
    ..The CoV in Stroop discriminated the performance of epsilon4 carriers from noncarriers in healthy older controls and the CoV in task switching was correlated with cerebrospinal fluid (CSF) biomarkers predictive of DAT...
  50. pmc Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer's disease pathology
    Jee Hoon Roh
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Sci Transl Med 4:150ra122. 2012
    ..Sleep-wake behavior and diurnal fluctuation of Aβ in the central nervous system may be functional and biochemical indicators, respectively, of Aβ-associated pathology...
  51. pmc Modulation of astrocyte glutamate transporters decreases seizures 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 37:764-71. 2010
    ..These results indicate that astrocyte glutamate transporters contribute to epileptogenesis in Tsc1(GFAP)CKO mice and suggest novel therapeutic strategies for epilepsy in TSC directed at astrocytes...
  52. 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...
  53. pmc Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease
    Carlos Cruchaga
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
    Arch Neurol 68:1013-9. 2011
    ..The linkage disequilibrium pattern around the APOE gene has made it difficult to determine whether all the association signal is derived from APOE or whether there is an independent signal from a nearby gene...
  54. ncbi request reprint Use of YFP to study amyloid-beta associated neurite alterations in live brain slices
    Robert P Brendza
    Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, MO 63110, USA
    Neurobiol Aging 24:1071-7. 2003
    ..This acute slice preparation model should prove to be a useful tool to explore the pathophysiology of Abeta-related axonal, dendritic, and synaptic dysfunction...
  55. 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...
  56. 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...
  57. pmc In vivo human apolipoprotein E isoform fractional turnover rates in the CNS
    Kristin R Wildsmith
    Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS ONE 7:e38013. 2012
    ..We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis...
  58. 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...
  59. pmc Antisense reduction of tau in adult mice protects against seizures
    Sarah L DeVos
    Department of Neurology, Hope Center for Neurological Disorders, Washington University, St Louis, Missouri 63110, USA
    J Neurosci 33:12887-97. 2013
    ....
  60. 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...
  61. 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...
  62. ncbi request reprint Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage
    Jin Moo Lee
    Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, MO 63110, USA
    J Neurol Sci 229:249-54. 2005
    ..These results suggest that increased vascular MMP-9 expression, stimulated by Abeta, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage (ICH) in patients with CAA...
  63. 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...
  64. pmc GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease
    Carlos Cruchaga
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 78:256-68. 2013
    ..67 × 10⁻⁴, 0.039, 4.86 × 10⁻⁵, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci...
  65. 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...
  66. 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...
  67. pmc Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis
    Joseph M Castellano
    Department of Neurology, Hope Center for Neurological Disorders, Charles F and Joanne Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 109:15502-7. 2012
    ..Together, our results suggest a unique mechanism by which LDLR regulates brain-to-blood Aβ clearance, which may serve as a useful therapeutic avenue in targeting Aβ clearance from the brain...
  68. pmc Opposing synaptic regulation of amyloid-β metabolism by NMDA receptors in vivo
    Deborah K Verges
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 31:11328-37. 2011
    ..NMDA receptor antagonists increase ISF Aβ levels, suggesting that basal activity at these receptors normally suppresses Aβ levels in vivo. This has implications for understanding normal Aβ metabolism as well as AD pathogenesis...
  69. 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...
  70. ncbi request reprint Role of caspase-3 in ethanol-induced developmental neurodegeneration
    Chainllie Young
    Department of Psychiatry, Campus Box 8134, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
    Neurobiol Dis 20:608-14. 2005
    ..We conclude that absence of functional caspase-3 alters the time course and morphological characteristics of the neurodegenerative process but does not prevent ethanol-induced neuron death...
  71. pmc Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease
    Rawan Tarawneh
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 70:274-85. 2011
    ..Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. Here we investigate CSF VILIP-1 and VILIP-1/amyloid-β42 (Aβ42) ratio as diagnostic and prognostic markers in early AD...
  72. pmc Evaluation of 5-ethynyl-2'-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system
    Chenbo Zeng
    Department of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110, USA
    Brain Res 1319:21-32. 2010
    ..for tracking the two populations of neurons generated at different time points. In conclusion, our results suggest that EdU staining is a fast, sensitive and reproducible method to study cell proliferation in the central nervous system...
  73. 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...
  74. pmc Early diffusion-weighted MRI as a predictor of caspase-3 activation after hypoxic-ischemic insult in neonatal rodents
    Michael F Wendland
    University California San Francisco, Department of Neurology, Box 0663, 521 Parnassus Ave, San Francisco, CA 94143 0663, USA
    Stroke 39:1862-8. 2008
    ..We asked whether the extent of injury depicted on DWI can predict the presence of caspase-3 activation, a quantitative marker of apoptotic injury, after hypoxia-ischemia (H-I) in postnatal day 7 rats...
  75. 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...
  76. 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
    ....
  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. 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
    ....
  79. 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...
  80. 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...
  81. 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
  82. 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...
  83. pmc Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system
    Robert D Bell
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Cereb Blood Flow Metab 27:909-18. 2007
    ..7-fold, whereas Abeta42 binding to apoJ enhanced Abeta42 BBB clearance rate by 83%. Thus, Abeta, apoE, and apoJ are cleared from brain by different transport pathways, and apoE and apoJ may critically modify Abeta clearance at the BBB...
  84. 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...
  85. 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...
  86. 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
  87. 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...
  88. 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...
  89. 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
    ....
  90. 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
    ....
  91. 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
    ....
  92. 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
    ....
  93. 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...
  94. 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...
  95. 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...
  96. 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...
  97. 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...
  98. 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
    ....
  99. 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)...
  100. 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
    ....
  101. 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...