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John Q. Trojanowski

Bio: John Q. Trojanowski is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Alzheimer's disease & Dementia. The author has an hindex of 226, co-authored 1467 publications receiving 213948 citations. Previous affiliations of John Q. Trojanowski include Vanderbilt University & University of California, San Francisco.


Papers
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Journal ArticleDOI
TL;DR: PC12 cells contain dissociated or incompletely assembled immunoreactive neurofilament triplet proteins and that these proteins can be induced by NGF, and are therefore an attractive model system not only for studies of neuronal differentiation but also for Studies of neurofilaments metabolism and disorders thereof.

87 citations

Journal ArticleDOI
TL;DR: Data suggest that αS, βS, and γS may play a functional role in the development and maturation of SN neurons, but it remains to be determined how sequestration of αS as LBs in PD contributes to the degeneration ofSN neurons.

87 citations

Journal ArticleDOI
TL;DR: The adult pattern of neuronal cytoskeletal protein expression in the hippocampus was attained by the second postnatal year for all proteins.
Abstract: In this study of the developing human hippocampus, we monitor the timing of onset and the sequential patterns of expression of 11 developmentally regulated proteins that are important components of the neuronal cytoskeleton. Immunohistochemistry using well-characterized antibodies was conducted with fixed paraffin-embedded sections from hippocampi at various stages of fetal and postnatal development. At 9 weeks gestational age, immunoreactivity was evident for the microtubule-associated proteins (MAPs), MAP2 and MAP5, low molecular weight (Mr) neurofilament (NF) protein (NF-L), poorly phosphorylated mid-Mr NF protein (NF-M/P−), vimentin, and α-and β-tubulins within the somatodendritic domain of neurons of the hippocampal plate. Weak immunoreactivity for moderately phosphorylated, high Mr NF protein (NF-H/P+), tau, and nestin was observed. Highly phosphorylated mid-Mr NF protein (NF-M/P+++) and α-internexin were first detected at 15 weeks and highly phosphorylated, high Mr NF protein (NF-H/P+++) at 20 weeks. At 15 weeks, MAP2, MAP5, and tubulins were expressed in an “inside-out” gradient and in a gradient between hippocampal subfields with subiculum > ammonic subfields > dentate gyrus. These gradients paralleled the maturational gradients seen in cytoarchitectural and neuronal morphologic studies. The adult pattern of neuronal cytoskeletal protein expression in the hippocampus was attained by the second postnatal year for all proteins. Our findings demonstrate an elaborate orchestration of cytoskeletal protein expression within the hippocampus that is qualitatively similar to what is seen in other brain regions and in nonhuman species but which also has some important differences in timing and pattern. The differences in the developmentally regulated expression of neuronal cytoskeletal proteins in separate regions of the central nervous system (CNS) suggest that there are region-specific differences in composition and function of the neuronal cytoskeleton. These observations have implications for understanding the role of the neuronal cytoskeleton in the developing, mature, and diseased CNS. © 1996 Wiley-Liss, Inc.

87 citations

Journal ArticleDOI
TL;DR: Clinical cases with FTLD-TDP andFTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF.
Abstract: Objective: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau). Methods: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD. Results: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. Conclusions: Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF.

87 citations

Journal ArticleDOI
TL;DR: These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLD-TAU, and emphasise the role of WM neuroim imaging for in vivo discrimination between FTLD -TAU andFTLD-TDP.
Abstract: Background Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI). Methods Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-oneout cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort. Results ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLDTAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP. Conclusions These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLDTAU, and emphasise the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.

87 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available.
Abstract: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

13,710 citations

Journal ArticleDOI
19 Jul 2002-Science
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Abstract: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer9s disease (AD) may be caused by deposition of amyloid β-peptide (Aβ) in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Aβ in the brain is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Aβ production and Aβ clearance.

12,652 citations

Journal ArticleDOI
TL;DR: There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

9,131 citations