Abstract:
OBJECTIVE:Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. METHODS:Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker. RESULTS:Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p ≤ 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p ≤ 0.006). Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD (p ≤ 0.0003). CONCLUSIONS:Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies.
journal_name
Neurologyjournal_title
Neurologyauthors
Goetzl EJ,Boxer A,Schwartz JB,Abner EL,Petersen RC,Miller BL,Kapogiannis Ddoi
10.1212/WNL.0000000000001702subject
Has Abstractpub_date
2015-07-07 00:00:00pages
40-7issue
1eissn
0028-3878issn
1526-632Xpii
WNL.0000000000001702journal_volume
85pub_type
杂志文章相关文献
NEUROLOGY文献大全abstract::In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition bo...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e31823a0ed3
更新日期:2011-11-29 00:00:00
abstract::In thymomas associated with myasthenia gravis (MG), the authors found that perivascular infiltrates of memory lymphocytes and mature dendritic cells (DCs) were more frequent in patients with early improvement after thymectomy than in patients without response to thymectomy. Although these findings may be limited to pa...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000174560.35190.84
更新日期:2005-09-13 00:00:00
abstract:OBJECTIVE:To determine the potential of detection in CSF of specific Borrelia burgdorferi antigen, OspA, as a marker of infection in neurologic Lyme disease and compare this with the detection of antibody. DESIGN:CSF from 83 neurologic patients in an area highly endemic for Lyme disease was examined prospectively for ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.45.11.2010
更新日期:1995-11-01 00:00:00
abstract::We conducted a randomized double-blind comparison of three doses of the novel antiepileptic drug (AED) topiramate (200, 400, and 600 mg/day) and placebo as adjunctive therapy in patients with refractory partial onset epilepsy receiving one or two other AEDs at therapeutic concentrations. A total of 181 patients comple...
journal_title:Neurology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1212/wnl.46.6.1684
更新日期:1996-06-01 00:00:00
abstract:OBJECTIVE:To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. METHODS:As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepat...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e31828726e1
更新日期:2013-03-12 00:00:00
abstract::We studied 13 patients with severe drug-induced parkinsonism (DIP) using L-6-[18F]fluorodopa positron emission tomography (18F-dopa PET) to investigate the integrity of their dopaminergic nigrostriatal projections. Twelve of these patients were subsequently followed clinically for a median of 23.5 months (range, 6 to ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.43.3_part_1.552
更新日期:1993-03-01 00:00:00
abstract::Unusual late-onset complications of brain irradiation, characterized by reversible neurologic focal signs, seizures, and MRI alterations, have recently been reported and classified as stroke-like migraine attacks after radiation therapy (SMART)(1) and peri-ictal pseudoprogression (PIPG).(2.) ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e3182a43b1f
更新日期:2013-09-10 00:00:00
abstract:OBJECTIVES:To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000000959
更新日期:2014-11-04 00:00:00
abstract::To evaluate possible progressive metabolic changes in Duchenne muscular dystrophy, we used 31P nuclear magnetic resonance spectroscopy to measure high-energy phosphate compounds and phosphorylated diesters (PDE) in resting gastrocnemius muscle of 14 Duchenne patients and 10 normal boys. The patients had higher inorgan...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.37.1.165
更新日期:1987-01-01 00:00:00
abstract::Antiacetylcholine receptor antibody (anti-AChR) was spontaneously synthesized by cultured thymic tissue from 19 of 35 patients with myasthenia gravis. Two other thymus cultures produced antibody after stimulation by pokeweed mitogen. Antibody production correlated with histologic evidence of thymitis, long duration of...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.31.8.935
更新日期:1981-08-01 00:00:00
abstract:BACKGROUND:In polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy, antibodies to myelin-associated glycoprotein (MAG), sulfoglucuronyl paragloboside (SGPG), and sulfatide have been associated with specific clinical and electrophysiologic features. However, it is not known whether the results of ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.56.2.228
更新日期:2001-01-23 00:00:00
abstract::We retrospectively studied the effects of changing antiepileptic drug levels on patterns of seizure discharge in 8 patients investigated with intracerebral electrodes during presurgical evaluation. We compared seizures recorded at high levels of medication to seizures recorded at low levels for changes in seizure dura...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.40.3_part_1.407
更新日期:1990-03-01 00:00:00
abstract::The authors examined the neural function of a postmeningitic deaf-blind patient who regained his hearing with a multichannel cochlear implant. Auditory stimuli activated the temporal cortices of both sides in a manner similar to that of controls, reflecting the successful recruitment of the auditory cortex after impla...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000234141.72891.13
更新日期:2006-09-12 00:00:00
abstract:BACKGROUND:Among patients with a patent foramen ovale (PFO) and a prior cryptogenic ischemic stroke or TIA, the absolute and relative risk of recurrent events is unclear. METHODS:We conducted a systematic review and meta-analysis of clinical studies in any language published up to February 2008. We included studies re...
journal_title:Neurology
pub_type: 杂志文章,meta分析,评审
doi:10.1212/WNL.0b013e3181aa2a19
更新日期:2009-07-14 00:00:00
abstract::Genetic factors are important in Alzheimer disease (AD) and Parkinson disease but have not been well characterized in Lewy body dementia (LBD). The authors obtained family history in patients from an autopsy series of AD and LBD and in living healthy controls. A family history of dementia was more common in both LBD a...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000219812.20616.b3
更新日期:2006-06-27 00:00:00
abstract:OBJECTIVE:Hospital readmission is an important quality improvement measure that has not been well-studied in pediatric neurology. We examined predictors of 7-day and 30-day readmissions for pediatric patients hospitalized with a neurologic diagnosis. METHODS:This was a retrospective study of hospital readmission rates...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000007280
更新日期:2019-04-16 00:00:00
abstract:OBJECTIVE:To determine the association between hypertensive disorders of pregnancy (HDP) and cognitive impairment 15 years after pregnancy, we measured cognitive performance in 115 women with a history of HDP and in 481 women with a previous normotensive pregnancy. METHODS:This was a nested cohort study embedded in a ...
journal_title:Neurology
pub_type: 评论,杂志文章
doi:10.1212/WNL.0000000000011363
更新日期:2021-02-02 00:00:00
abstract::There are several reports of a defect of complex I in the substantia nigra (SN) of Parkinson's disease (PD) patients. To evaluate whether this is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative phosphorylation (OXPHOS) system, we measur...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.43.11.2262
更新日期:1993-11-01 00:00:00
abstract:OBJECTIVE:To use the large dataset from the Tysabri Outreach: Unified Commitment to Health (TOUCH) program to compare progressive multifocal leukoencephalopathy (PML) risk with natalizumab extended interval dosing (EID) vs standard interval dosing (SID) in patients with multiple sclerosis (MS). METHODS:This retrospect...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000008243
更新日期:2019-10-08 00:00:00
abstract::Call-Fleming syndrome is a reversible segmental vasoconstriction of cerebral arteries manifested by a "thunderclap" headache and focal neurologic symptoms. Although of unknown etiology, it has been reported in association with vasoactive sympathomimetic drugs. The authors report Call-Fleming syndrome in two patients w...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000223648.76430.27
更新日期:2006-07-11 00:00:00
abstract::The behavioral and anatomic correlates of pure alexia were analyzed in 16 patients. Right homonymous hemianopia failed to appear in three patients, who had right achromatopsia instead. Color anomia and unilateral optic ataxia were seen in six patients. Memory defects were found in two patients. Visual agnosia was note...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.33.12.1573
更新日期:1983-12-01 00:00:00
abstract::A 12-year-old girl presented with headache, nausea, decreased level of consciousness, and diplopia. Brain MRI, arteriography (figure e-1 on the Neurology® Web site at www.neurology.org), vasculitic markers, and CSF were normal, as were EEGs and ECGs. Transcranial color-coded ultrasonography of the basilar artery revea...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000436064.90018.48
更新日期:2013-11-19 00:00:00
abstract::Cisplatin, used to treat ovarian, bladder, and testicular cancers, causes a sensory dose-limiting neuropathy. Preliminary observations in humans and animals suggest that nerve damage may be prevented by ACTH analogs, particularly those belonging to the melanocortin class, and by nerve growth factor (NGF). We establish...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.44.3_part_1.488
更新日期:1994-03-01 00:00:00
abstract:OBJECTIVE:To assess the genetic contribution of TBK1, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, in Belgian FTD and ALS patient cohorts containing a significant part of genetically unresolved patients. METHODS:We sequenced TBK1 in a hospital-based cohort of 48...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000002220
更新日期:2015-12-15 00:00:00
abstract::Subsequent to publication of the NINDS t-PA Stroke Study results, we sought to determine the proportion of patients eligible for and receiving intravenous tissue plasminogen activator (t-PA) at an active acute stroke treatment center. Over a 12-month period there were 185 stroke code activations. Of these, 134 involve...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.50.2.501
更新日期:1998-02-01 00:00:00
abstract::Subacute encephalitis, characterized by demyelination, gliosis of the gray and white matter, focal necrosis, microglial nodules, atypical oligodendrocyte nuclei, and multinucleation of cells, was present in 27 of 30 (90%) autopsied patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex. Subac...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.37.4.562
更新日期:1987-04-01 00:00:00
abstract::Stenosis or occlusion of the major arteries of the head and neck may cause hemodynamic impairment of the distal cerebral circulation. Hemodynamic factors may play an important role in the pathogenesis of ischemic stroke for patients with cerebrovascular disease. Several neuroimaging methods are currently available for...
journal_title:Neurology
pub_type: 杂志文章,评审
doi:10.1212/wnl.53.2.251
更新日期:1999-07-22 00:00:00
abstract::Alzheimer disease (AD) has a significant impact on caregivers. Administering and managing medications is one of their many daily tasks. More effective modes of drug administration may benefit patient and caregiver, and may improve compliance. A prospective outcome of the IDEAL (Investigation of TransDermal Exelon in A...
journal_title:Neurology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1212/01.wnl.0000281848.25142.11
更新日期:2007-07-24 00:00:00
abstract:OBJECTIVE:Current prehospital scales used to detect large vessel occlusion reveal very low endovascular thrombectomy (EVT) rates among selected patients. We developed a novel prehospital scale, the Madrid-Direct Referral to Endovascular Center (M-DIRECT), to identify EVT candidates for direct transfer to EVT-capable ce...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000008998
更新日期:2020-02-25 00:00:00
abstract:OBJECTIVE:To investigate long-term employment outcomes after resective epilepsy surgery in a national population-based cohort of adults. METHODS:In the Swedish National Epilepsy Surgery Register, all adults who were operated with resective epilepsy surgery from 1995 to 2010 were identified. Two-year follow-up was avai...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000002069
更新日期:2015-10-27 00:00:00