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排序方式: 共有790条查询结果,搜索用时 15 毫秒
1.
Karen Nuytemans PhD Vanessa Inchausti BS Gary W. Beecham PhD Liyong Wang PhD Dennis W. Dickson MD John Q. Trojanowski MD PhD Virginia M.‐Y. Lee PhD Deborah C. Mash PhD Matthew P. Frosch MD PhD Tatiana M. Foroud PhD Lawrence S. Honig MD PhD Thomas J. Montine MD PhD Ted M. Dawson MD PhD Eden R. Martin PhD William K. Scott PhD Jeffery M. Vance MD PhD 《Movement disorders》2014,29(6):827-830
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3.
Jon B. Toledo Ane Korff Leslie M. Shaw John Q. Trojanowski Jing Zhang 《Acta neuropathologica》2013,126(5):683-697
Alzheimer’s disease (AD) and Lewy body diseases (LBD), e.g., Parkinson’s disease (PD) dementia and dementia with Lewy bodies (DLB), are common causes of geriatric cognitive impairments. In addition, AD and LBD are often found in the same patients at autopsy; therefore, biomarkers that can detect the presence of both pathologies in living subjects are needed. In this investigation, we report the assessment of α-synuclein (α-syn) in cerebrospinal fluid (CSF) and its association with CSF total tau (t-tau), phosphorylated tau181 (p-tau181), and amyloid beta1-42 (Aβ1-42) in subjects of the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 389), with longitudinal clinical assessments. A strong correlation was noted between α-syn and t-tau in controls, as well as in patients with AD and mild cognitive impairment (MCI). However, the correlation is not specific to subjects in the ADNI cohort, as it was also seen in PD patients and controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI; n = 102). A bimodal distribution of CSF α-syn levels was observed in the ADNI cohort, with high levels of α-syn in the subjects with abnormally increased t-tau values. Although a correlation was also noted between α-syn and p-tau181, there was a mismatch (α-syn–p-tau181-Mis), i.e., higher p-tau181 levels accompanied by lower α-syn levels in a subset of ADNI patients. We hypothesize that this α-syn–p-tau181-Mis is a CSF signature of concomitant LBD pathology in AD patients. Hence, we suggest that inclusion of measures of CSF α-syn and calculation of α-syn–p-tau181-Mis improves the diagnostic sensitivity/specificity of classic CSF AD biomarkers and better predicts longitudinal cognitive changes. 相似文献
4.
J Q Trojanowski M L Schmidt L Otvos R C Gur R E Gur H Hurtig V M Lee 《Annals of medicine》1989,21(2):113-116
Here we review our recent "epitope analyses" of a few of the fibrous intraneuronal inclusions that are distinctive hallmarks of human neurodenerative conditions using a large library of monoclonal antibodies (MAbs) raised to normal neuronal cytoskeletal proteins. Analyses of the low (NF-L), middle (NF-M), and high (NF-M), and high (NF-H) molecular weight neurofilament (NF) proteins with greater than 500 MAbs enumerated epitopes shared by NF proteins and the intraneuronal neurofibrillary tangles (NFTs) that occur in the hippocampus and brainstem of Alzheimer's disease (AD) subjects. We identified the NF-H multi-phosphorylation repeat domain, i.e. repeats of Lys-Ser-Pro-X (where X is a small uncharged amino acid and Ser acts as a phosphate acceptor), as the determinant recognized by 15/16 MAbs that detected NFTs in sections of AD hippocampus, and 11 of the same 16 MAbs recognised NF-M multi-phosphorylation repeats. Further, the antigen binding regions of these MAbs were shown to comprise 13 separate classes based on their differential binding to 12 synthetic peptides derived from the NF-H and NF-M multi-phosphorylation sites, NF subunits of 10 diverse mammalian and sub-mammalian species, and normal human tau (tau). None of these anti-NF MAbs recognized NFTs in the brainstem of subjects with progressive supranuclear palsy (PSP), but NFTs in AD brainstem sections were reactive with five of these MAbs. Both PSP and AD brainstem NFTs were recognized by MAbs specific for tau and paired helical filament antigens.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
5.
Anli Liu Kelly Werner Subhojit Roy John Q. Trojanowski Ursula Morgan-Kane Bruce L. Miller 《Neurocase》2013,19(3):235-247
Patients presenting with left-sided FTLD syndromes sometimes develop a new preoccupation with art, greater attention to visual stimuli, and increased visual creativity. We describe the case of a 53-year-old, right-handed man with a history of bipolar disorder who presented with language and behavior impairments characteristic of FTLD, then developed motor symptoms consistent with a second diagnosis of amyotrophic lateral sclerosis. Though the patient had never created visual art before, he developed a compulsion for painting beginning at the earliest stages of his disease, and continued producing art daily until he could no longer lift a paintbrush because of his motor deficits. Upon autopsy, he was found to have ubiquitin and TDP43-positive inclusions with MND pathology. This case study details the patient's longitudinal neuropsychological, emotional, behavioral, and motor symptoms, along with structural imaging, neurologic, and neuropathologic findings. Multiple examples of the patient's art are depicted throughout all stages of his illness, and the possible cognitive, behavioral, and neurologic correlates of his new-onset visual artistry are discussed. 相似文献
6.
Brit Mollenhauer Chelsea J. Caspell‐Garcia Christopher S. Coffey Peggy Taylor Andy Singleton Leslie M. Shaw John Q. Trojanowski Mark Frasier Tanya Simuni Alex Iranzo Wolfgang Oertel Andrew Siderowf Daniel Weintraub John Seibyl Arthur W. Toga Caroline M. Tanner Karl Kieburtz Lana M. Chahine Kenneth Marek Douglas Galasko 《Movement disorders》2019,34(9):1354-1364
7.
David Coughlin Sharon X. Xie Mendy Liang Andrew Williams Claire Peterson Daniel Weintraub Corey T. McMillan David A. Wolk Rizwan S. Akhtar Howard I. Hurtig H. Branch Coslett Roy H. Hamilton Andrew D. Siderowf John E. Duda Katya Rascovsky Edward B. Lee Virginia M.‐Y. Lee Murray Grossman John Q. Trojanowski David J. Irwin 《Annals of neurology》2019,85(2):259-271
8.
Longitudinal Change of Clinical and Biological Measures in Early Parkinson's Disease: Parkinson's Progression Markers Initiative Cohort 下载免费PDF全文
Tanya Simuni MD Andrew Siderowf MD MSCE Shirley Lasch BS MBA Chris S. Coffey PhD Chelsea Caspell‐Garcia MS Danna Jennings MD Caroline M. Tanner MD PhD John Q. Trojanowski MD PhD Leslie M. Shaw PhD John Seibyl MD Norbert Schuff PhD Andrew Singleton PhD Karl Kieburtz MD MPH Arthur W. Toga PhD Brit Mollenhauer MD Doug Galasko MD Lana M. Chahine MD Daniel Weintraub MD Tatiana Foroud PhD Duygu Tosun PhD Kathleen Poston MD MS Vanessa Arnedo Mark Frasier PhD Todd Sherer PhD Sohini Chowdhury Kenneth Marek MD the Parkinson's Progression Marker Initiative 《Movement disorders》2018,33(5):771-782
Objective: The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD. Methods: We describe 5‐year longitudinal change of the MDS‐UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123‐I Ioflupane striatal binding and correlation between the 2 measures. Results: A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS‐UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for the change over time), with a steeper change in year 1. Dopaminergic therapy had a significant effect on the change of MDS‐UPDRS. There was a significant longitudinal change in dopamine transporter binding in all striatal regions (P < .001). There was a significant but weak correlation between MDS‐UPDRS and dopamine transporter binding at baseline and years 1, 2, and 4, but no correlation between the rate of change of the 2 variables. Conclusions: We present 5‐year longitudinal data on the change of the MDS‐UPDRS and other clinical and dopamine transporter imaging outcome measures in early PD. These data can be used for sample size estimates for interventional studies in the de novo PD population. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. 相似文献
9.
Rachael Purri BA Laura Brennan PhD Jacqueline Rick PhD Sharon X. Xie PhD Benjamin L. Deck BS Lana M. Chahine MD Nabila Dahodwala MD Alice Chen-Plotkin MD John E. Duda MD James F. Morley MD PhD Rizwan S. Akhtar MD PhD John Q. Trojanowski MD PhD Andrew Siderowf MD MSCE Daniel Weintraub MD 《Movement disorders》2020,35(9):1618-1625
10.
Novel conformation‐selective alpha‐synuclein antibodies raised against different in vitro fibril forms show distinct patterns of Lewy pathology in Parkinson's disease 下载免费PDF全文