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.

Neurotrophin Receptor TrkC Predicts Good Clinical Outcome in Medulloblastoma and Other Primitive Neuroectodermal Brain Tumors

Abstract: Background: Neurotrophins and their cognate receptors TrkA, TrkB and TrkC regulate proliferation, differentiation and death of neuronal progenitor cells and may be implicated in the progression of medulloblastoma and other primitive neuroectodermal brain tumors (PNET). These common childhood brain tumors are composed of morphologically undifferentiated cells that have important similarities to neuroectodermal progenitor cells of the developing CNS. Patients and Methods: To identify biologic prognostic factors in childhood PNET we determined expression levels of TrkC mRNA in tumor samples from 87 PNET patients by in situ hybridization. Comparison of TrkC mRNA expression levels with clinical variables was performed using univariate and multivariable Cox regression analysis. Results: Cox regression analysis revealed that children with tumors expressing no or little TrkC mRNA had a 4.8-fold (p < 0.00005) greater risk of death than children with tumors with high TrkC mRNA expression. This hazard ratio remained consistent after adjusting for clinical variables. Five-year survival was 89% for patients with PNETs expressing high levels of TrkC mRNA and 47% for patients with PNETs expressing little or no levels of TrkC mRNA (log rank; p < 0.00005). Conclusions: The TrkC neurotrophin receptor appears to be a powerful independent prognostic factor in PNET and may have a role in patient assignment to risk-based treatment strategies.

Delayed transplantation of human neurons following brain injury in rats: a long-term graft survival and behavior study.

Abstract: The NTera2 (NT2) cell line is a homogeneous population of cells, which, when treated in vitro with retinoic acid, terminally differentiate into postmitotic neuronal NT2N cells. Although NT2N neurons transplanted in the acute (24 h postinjury) period survive for up to 1 month following experimental traumatic brain injury (TBI), nothing is known of their ability to survive for longer periods or of their effects when engrafted during the chronic postinjury period. Adult male Sprague-Dawley rats (n = 348; 360-400 g) were initially anesthetized and subjected to severe lateral fluid-percussion (FP) brain injury or sham injury. At 1 month postinjury, only brain-injured animals showing severe neurobehavioral deficits received cryopreserved NT2N neurons stereotaxically transplanted into three sites in the peri-injured cortex (n = 18). Separate groups of similarly brain-injured rats received human fibroblast cells (n = 13) or cell suspension vehicle (n = 14). Sham-injured animals (no brain injury) served as controls and received NT2N transplants (n = 24). All animals received daily immunosuppression for three months. Behavioral testing was performed at 1, 4, 8, and 12 weeks post-transplantation, after which animals were sacrificed for histological analysis. Nissl staining and anti-human neuronal specific enolase (NSE) immunostaining revealed that NT2N neurons transplanted in the chronic post-injury period survived up to 12 weeks post-transplantation, extended processes into the host cortex and immunolabeled positively for synaptophysin. There were no statistical differences in cognitive or motor function among the transplanted brain-injured groups. Long-term graft survival suggests that NT2N neurons may be a viable source of neural cells for transplantation after TBI and also that these grafts can survive for a prolonged time and extend processes into the host cortex when transplanted in the chronic post-injury period following TBI.

Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative

Abstract: Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.

The Impact of Exercise, Cognitive Activities, and Socialization on Cognitive Function: Results From the National Long-Term Care Survey.

Abstract: Currently, there are no effective treatments for Alzheimer’s disease and related disorders and age continues to be a robust risk factor. Thus, population aging in the United States may have catastrophic results if interventions are not found and implemented. This study examines possible associations between cognitive impairment and exercise, cognitive activities, and socialization. Cognitive activities, socialization, and exercise were assessed at baseline, and cognitive function was measured at baseline, 5-year, and 10-year follow-up. Controlling for baseline cognitive function, age, sex, education, diabetes, and hypertension, linear regression was performed. Engagement in cognitive activities was inversely associated with the onset of cognitive impairment at 5-year follow-up but was no longer significant at 10-year follow-up. Exercise was associated with a lower risk of cognitive impairment at 10-year follow-up but was not significant at 5-year follow-up. Associations with socialization were not statistically significant at either follow-up.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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。

The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

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.

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics

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.

Free Radicals in the Physiological Control of Cell Function

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...