Affiliation: University of Pittsburgh
- Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementiaWilliam E Klunk
University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Neurobiol Aging 32:S20-36. 2011....
- Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer's disease brain but not in transgenic mouse brainWilliam E Klunk
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
J Neurosci 25:10598-606. 2005....
- Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigreesWilliam E Klunk
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
J Neurosci 27:6174-84. 2007..The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms...
- Two-year follow-up of amyloid deposition in patients with Alzheimer's diseaseWilliam E Klunk
University of Pittsburgh Medical School Pittsburgh, MA, USA
Brain 129:2805-7. 2006
- The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferationWilliam E Klunk
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Curr Opin Neurol 21:683-7. 2008....
- Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's diseaseOscar L Lopez
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Neuropsychiatry Clin Neurosci 15:346-53. 2003..Education and race were independently associated with psychosis. However, while education was associated with psychosis in mild/moderate stages, race was associated with psychosis in moderate/severe stages...
- Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's diseaseMilos D Ikonomovic
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Brain 131:1630-45. 2008..The strong direct correlation of in vivo PiB retention with region-matched quantitative analyses of Abeta plaques in the same subject supports the validity of PiB-PET imaging as a method for in vivo evaluation of Abeta plaque burden...
- Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer diseaseClayton A Wiley
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
Arch Neurol 66:60-7. 2009..Because postmortem histopathological analyses are limited to single end-stage assessment, the time course and nature of this relationship are not well understood...
- Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibitionOscar L Lopez
Alzheimer s Disease Research Center and Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Am Geriatr Soc 53:83-7. 2005..To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes...
- Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivativeWilliam E Klunk
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA
J Neuropathol Exp Neurol 61:797-805. 2002....
- Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid imaging studies in Alzheimer's diseaseScott K Ziolko
Department of Radiology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Rm. B-938, PA 15213, USA
Neuroimage 33:94-102. 2006..These results indicate that voxel-based methods will be useful for future larger longitudinal studies of amyloid deposition that could improve AD diagnosis and anti-amyloid therapy assessment...
- Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-BWilliam E Klunk
Department of Psychiatry, PET Facility, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213-2582, USA
Ann Neurol 55:306-19. 2004..This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects...
- Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserveAnn D Cohen
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
J Neurosci 29:14770-8. 2009....
- Consideration of optimal time window for Pittsburgh compound B PET summed uptake measurementsREBECCA L MCNAMEE
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
J Nucl Med 50:348-55. 2009..In this work, regional PiB SUVRs were examined across 9 time windows to select the window that provided the best trade-offs between bias, correlation, and effective contrast...
- Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with Pittsburgh Compound BCyrus A Raji
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 2593, United States
J Neurosci Methods 172:277-82. 2008..02, p=0.01) and anterior ventral striatum [t(9)=2.37, p=0.04] in AD. No group differences (AD versus MCI) were detected in laterality [F (1, 15)=0.15, p=0.7] or asymmetry [F (1, 15)=0.7, p=0.42]...
- Apolipoprotein D is a component of compact but not diffuse amyloid-beta plaques in Alzheimer's disease temporal cortexPurnima P Desai
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
Neurobiol Dis 20:574-82. 2005..Elevated apoD in AD brain may influence Abeta aggregation, or facilitate phagocytosis and transport of Abeta fibrils from plaques to cerebral vasculature...
- Apolipoprotein E and alpha-1-antichymotrypsin genotypes do not predict time to psychosis in Alzheimer's diseaseRobert A Sweet
Department of Psychiatry, School of Medicine, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, USA
J Geriatr Psychiatry Neurol 15:24-30. 2002..The findings support the hypothesis that these two genetic determinants of AD risk do not contribute to the risk of development of psychotic symptoms in AD...
- Frequent amyloid deposition without significant cognitive impairment among the elderlyHoward Jay Aizenstein
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Arch Neurol 65:1509-17. 2008....
- X-34 labeling of abnormal protein aggregates during the progression of Alzheimer's diseaseMilos D Ikonomovic
Department of Neurology and Psychiatry, University of Pittsburgh, Pennsylvania 15213, USA
Methods Enzymol 412:123-44. 2006....
- PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PETSriram Venneti
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Neurobiol Aging 30:1217-26. 2009....
- Whatever happened to Pittsburgh Compound-A?William E Klunk
Department of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Alzheimer Dis Assoc Disord 22:198-203. 2008
- Impact of amyloid imaging on drug development in Alzheimer's diseaseChester A Mathis
Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
Nucl Med Biol 34:809-22. 2007....
- Synthesis and beta-amyloid binding properties of rhenium 2-phenylbenzothiazolesKuo Shyan Lin
Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Bioorg Med Chem Lett 19:2258-62. 2009....
- Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-BMeryl A Butters
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA
Alzheimer Dis Assoc Disord 22:261-8. 2008..Our findings are consistent with and supportive of the hypothesis that depression may herald the development of AD in some individuals...
- A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brainChester A Mathis
PET Facility, Department of Radiology, University of Pittsburgh, PA 15213, USA
Bioorg Med Chem Lett 12:295-8. 2002..Amyloid deposits were imaged with multiphoton microscopy in the brains of living transgenic mice following the systemic injection of unlabeled 6. [(11)C]6 is a promising amyloid imaging agent for Alzheimer's disease...
- Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysisBrian J Lopresti
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
J Nucl Med 46:1959-72. 2005..This work reports on simplified methods of analysis for human PIB imaging...
- Amyloid imaging in mild cognitive impairment subtypesDavid A Wolk
Alzheimer s Disease Research Center, University of Pittsburgh, Pittsburgh, PA 19104, USA
Ann Neurol 65:557-68. 2009....
- Effects of lipophilicity on the affinity and nonspecific binding of iodinated benzothiazole derivativesYanming Wang
P E T Facility, Department of Radiology, Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
J Mol Neurosci 20:255-60. 2003..These results provide important SAR information to guide the development of novel amyloid-binding agents and provide further insights into the molecular interaction between 2-aryl benzothiazole ligands and Abeta fibrils...
- The binding of 2-(4'-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid componentWilliam E Klunk
Laboratory of Molecular Neuropharmacology, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
J Neurosci 23:2086-92. 2003..Finally, BTA-1 did not appear to bind significantly to common neuroreceptors or transporter sites. These data suggest that the binding of BTA-1 to AD brain is dominated by a specific interaction with Abeta amyloid deposits...
- Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's disease: correlation with cognitive impairmentSteven T DeKosky
Department of Neurology and the Alzheimer s Disease Research Center, University of Pittsburgh, PA, USA
Ann Neurol 53:81-90. 2003....
- Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agentsChester A Mathis
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
J Med Chem 46:2740-54. 2003..The encouraging in vitro and in vivo properties of [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition...
- Synthesis and evaluation of 2-(3'-iodo-4'-aminophenyl)-6-hydroxybenzothiazole for in vivo quantitation of amyloid deposits in Alzheimer's diseaseYanming Wang
PET Facility, Department of Radiology, School of Medicine, University of Pittsburgh, PA 15213, USA
J Mol Neurosci 19:11-6. 2002..43+/-0.62%ID/g detected in the whole brain at 2 min post i.v. injection. At 30 min, the radioactivity concentration decreased to 0.40+/-0.05%ID/g, indicating good clearance in the absence of amyloid deposits in the brain...
- Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathologyRobert A Sweet
Department of Psychiatry, Division of Geriatrics, Neuropsychiatry, University of Pittsburgh School of Medicine, PA, USA
Neurobiol Aging 23:547-53. 2002..Although AD+P has been inconsistently associated with more severe neuropathology, no prior studies have examined measures of neuronal and synaptic integrity...
- Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-BJulie C Price
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
J Cereb Blood Flow Metab 25:1528-47. 2005..This study also showed that it is feasible to perform quantitative PIB PET imaging studies that are needed to validate simpler methods for routine use across the AD disease spectrum...
- Blood and CSF biomarkers for AD revisited: what's new, what's good, and is this where we should be looking?William E Klunk
Laboratory of Molecular Neuropharmacology, Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213, USA
Neurobiol Aging 23:517-9; discussion 521-2. 2002
- Imaging the pathology of Alzheimer's disease: amyloid-imaging with positron emission tomographyWilliam E Klunk
Laboratory of Molecular Neuropharmacology, Department of Psychiatry, University of Pittsburgh School of Medicine, 705 Parran Hall, Pittsburgh, PA 15213, USA
Neuroimaging Clin N Am 13:781-9, ix. 2003..The capability to use positron emission tomography and selective markers for amyloid protein deposition promises to substantially alter the way we diagnosis and manage patients who have AD...
- Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer's disease from 1983 to 2000Oscar L Lopez
Alzheimer s Disease Research Center, University of Pittsburgh School of Medicine, Pennsylvania, USA
J Neuropsychiatry Clin Neurosci 15:67-73. 2003..g., aggression, agitation) and sleep disorders in AD. Although the use of SHA has a proven deleterious effect on patients with AD, their use has increased over the past two decades...
- Imaging technology for neurodegenerative diseases: progress toward detection of specific pathologiesChester A Mathis
Department of Neurology, University of Pittsburgh and Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA
Arch Neurol 62:196-200. 2005....
- Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementiaEllen M Whyte
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Am J Geriatr Psychiatry 10:321-7. 2002..In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment...
- Measuring target effect of proposed disease-modifying therapies in Alzheimer's diseaseRandall J Bateman
Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Neurotherapeutics 5:381-90. 2008..This review covers the current methods and technologies used in the therapeutic translation of proposed disease-modifying therapies for AD...
- Imaging amyloid-beta deposits in vivoBrian J Bacskai
Alzheimer Research Unit, Massachusetts General Hospital, Charlestown 02129, USA
J Cereb Blood Flow Metab 22:1035-41. 2002..This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques...
- Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenanceTristan Bolmont
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
J Neurosci 28:4283-92. 2008..These results indicate a role for microglia in plaque maintenance and provide a model with multiple targets for therapeutic intervention...
- Biopsy support for the validity of Pittsburgh compound B positron emission tomography with a twistWilliam E Klunk
Arch Neurol 65:1281-3. 2008
- 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairmentClifford R Jack
Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Brain 131:665-80. 2008..PiB and MRI provided complementary information such that clinical diagnostic classification using both methods was superior to using either in isolation...
- In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markersEvgueni E Nesterov
Department of Chemistry and Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Angew Chem Int Ed Engl 44:5452-6. 2005
- The role of biomarkers in clinical trials for Alzheimer diseaseLeon J Thal
University of California San Diego, Department of Neurosciences, La Jolla, California, USA
Alzheimer Dis Assoc Disord 20:6-15. 2006..Additionally, biochemical biomarkers in blood or cerebrospinal fluid are assessed. Currently appropriate uses of biomarkers in the study of Alzheimer disease, and areas where additional work is needed, are discussed...
- Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic miceRobert P Brendza
Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Clin Invest 115:428-33. 2005..This analysis suggests that ongoing axonal and dendritic damage is secondary to Abeta and is, in part, rapidly reversible...
- Development of a PET/SPECT agent for amyloid imaging in Alzheimer's diseaseYanming Wang
Department of Medicinal Chemistry and Pharmacology, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
J Mol Neurosci 24:55-62. 2004..These results suggest that the new radioiodinated benzothiazole ligand might be useful as a surrogate marker for the in vivo quantitation of amyloid deposition in human brain for use with either PET or SPECT...
- Targeting prion amyloid deposits in vivoMarcin Sadowski
Department of Neurology, New York University School of Medicine, New York, New York 10016, USA
J Neuropathol Exp Neurol 63:775-84. 2004..These results suggest that methoxy-X04 or similar derivatives could be used as PET imaging agents to improve the diagnosis of human prion diseases associated with amyloid deposition...
- Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case reportBrian J Bacskai
MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Charlestown, MA 02129, USA
Arch Neurol 64:431-4. 2007..Imaging revealed marked region specific binding of PiB and abnormal fluorodeoxyglucose uptake. Intervention Autopsy was performed 3 months after the PiB scan...
- Using a reference tissue model with spatial constraint to quantify [11C]Pittsburgh compound B PET for early diagnosis of Alzheimer's diseaseYun Zhou
The Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 0807, USA
Neuroimage 36:298-312. 2007..For pixel-wise quantification, due to the high noise level of pixel kinetics, the parametric images generated by RTM with conventional linear or nonlinear regression may be too noisy for use in clinical studies...
- Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humansAnne 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...
- Imaging of amyloid burden and distribution in cerebral amyloid angiopathyKeith A Johnson
Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
Ann Neurol 62:229-34. 2007....
- Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's diseaseKerryn E Pike
School of Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne, Australia
Brain 130:2837-44. 2007..The data also suggests that early intervention trials for AD targeted to non-demented individuals with cerebral Abeta deposition are warranted...
- Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer's diseaseAlexander Drzezga
Department of Nuclear Medicine, Technische Universitat, Munchen, Ismaninger Str 22, D 81675 Munich, Germany
Neuroimage 39:619-33. 2008....
- Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-beta ligand in transgenic miceBrian J Bacskai
Department of Neurology Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 100:12462-7. 2003..WT mice showed rapid brain entry and clearance of PIB without any binding. These results demonstrate that the compound PIB has the properties required for a good amyloid-imaging agent in humans with or at risk for AD...
- Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memoryRandy L Buckner
Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63105, USA
J Neurosci 25:7709-17. 2005..These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment...
- Chrysamine G and its derivative reduce amyloid beta-induced neurotoxicity in miceKazuhiro Ishii
Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Tokyo 156-8585, Japan
Neurosci Lett 333:5-8. 2002..1-1 microM, indicating that the mechanism of action for CG was not due to its chelating activity, but rather due to its anti-oxidant activity...
- Amyloid-Lowering Small Molecule AB-Binding Agents in ADWilliam Klunk; Fiscal Year: 2007..This team combines expertise in medicinal and radiochemistry, neuropharmacology, pharmacokinetics and drug metabolism, histopathology, molecular biology of amyloid, clinical trial design and clinical neurology and psychiatry. ..
- AMYLOID PATHOLOGY AND COGNITION IN NORMAL ELDERLYWilliam Klunk; Fiscal Year: 2007..We will complete 24 month follow-up on 15 65-69 y/o, 25 75-79 y/o and 25 80-84 y/o subjects. Subjects identified as amyloid-positive at 24 months will be followed yearly in years four and five. ..
- PET TRACERS TO MONITOR VACCINE AND IMMUNE THERAPY FOR ADWilliam Klunk; Fiscal Year: 2005....
- PET IMAGING PROBES FOR AMYLOID IN ALZHEIMERS AND AGINGWilliam Klunk; Fiscal Year: 2005....