Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.


IMPORTANCE:The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. OBJECTIVE:To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS:A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES:Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS:Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (β = 598.7, P < .001). CONCLUSIONS AND RELEVANCE:Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.


JAMA Neurol


JAMA neurology


Zetterberg H,Skillbäck T,Mattsson N,Trojanowski JQ,Portelius E,Shaw LM,Weiner MW,Blennow K,Alzheimer’s Disease Neuroimaging Initiative.




Has Abstract


2016-01-01 00:00:00














  • Association Between Cardiovascular Disease and Long-term Exposure to Air Pollution With the Risk of Dementia.

    abstract:Importance:Emerging yet contrasting evidence associates air pollution with incident dementia, and the potential role of cardiovascular disease (CVD) in this association is unclear. Objective:To investigate the association between long-term exposure to air pollution and dementia and to assess the role of CVD in that as...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Grande G,Ljungman PLS,Eneroth K,Bellander T,Rizzuto D

    更新日期:2020-07-01 00:00:00

  • Research Gaps and Controversies in Chronic Traumatic Encephalopathy: A Review.

    abstract:Importance:Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic ...

    journal_title:JAMA neurology

    pub_type: 杂志文章,评审


    authors: Asken BM,Sullan MJ,DeKosky ST,Jaffee MS,Bauer RM

    更新日期:2017-10-01 00:00:00

  • Association of pituitary adenylate cyclase-activating polypeptide with cognitive decline in mild cognitive impairment due to Alzheimer disease.

    abstract:IMPORTANCE:There is a deficit of pituitary adenylate cyclase-activating polypeptide (PACAP) in patients with neuropathologically confirmed Alzheimer dementia. However, whether this deficit is associated with the earlier stages of Alzheimer disease (AD) is unknown. This study was conducted to clarify the association bet...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Han P,Caselli RJ,Baxter L,Serrano G,Yin J,Beach TG,Reiman EM,Shi J

    更新日期:2015-03-01 00:00:00

  • Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy.

    abstract:Importance:YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. Objectives:To review the clinical...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Sommerville EW,Ng YS,Alston CL,Dallabona C,Gilberti M,He L,Knowles C,Chin SL,Schaefer AM,Falkous G,Murdoch D,Longman C,de Visser M,Bindoff LA,Rawles JM,Dean JCS,Petty RK,Farrugia ME,Haack TB,Prokisch H,McFarland R

    更新日期:2017-06-01 00:00:00

  • Serum Neurofilament Light Chain for Prognosis of Outcome After Cardiac Arrest.

    abstract:Importance:Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective:To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Des...

    journal_title:JAMA neurology

    pub_type: 杂志文章,多中心研究


    authors: Moseby-Knappe M,Mattsson N,Nielsen N,Zetterberg H,Blennow K,Dankiewicz J,Dragancea I,Friberg H,Lilja G,Insel PS,Rylander C,Westhall E,Kjaergaard J,Wise MP,Hassager C,Kuiper MA,Stammet P,Wanscher MCJ,Wetterslev J,Erl

    更新日期:2019-01-01 00:00:00

  • A 2-Step Cerebrospinal Algorithm for the Selection of Frontotemporal Lobar Degeneration Subtypes.

    abstract:Importance:Cerebrospinal fluid (CSF) core Alzheimer disease (AD) biomarkers have shown an excellent capacity for the in vivo detection of AD. Previous studies have shown that CSF levels of phosphorylated tau (p-tau) also correlate with tau pathology in frontotemporal lobar degeneration (FTLD) after accounting for AD co...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Lleó A,Irwin DJ,Illán-Gala I,McMillan CT,Wolk DA,Lee EB,Van Deerlin VM,Shaw LM,Trojanowski JQ,Grossman M

    更新日期:2018-06-01 00:00:00

  • Clinical Characteristics of Patients With Double-Seronegative Myasthenia Gravis and Antibodies to Cortactin.

    abstract:IMPORTANCE:Double-seronegative myasthenia gravis (dSNMG) includes patients with myasthenia gravis (MG) without detectable antibodies to the nicotinic acetylcholine receptor (AChR) or to muscle-specific tyrosine kinase (MuSK). The lack of a biomarker hinders the diagnosis and clinical management in these patients. Corta...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Cortés-Vicente E,Gallardo E,Martínez MÁ,Díaz-Manera J,Querol L,Rojas-García R,Illa I

    更新日期:2016-09-01 00:00:00

  • Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

    abstract:OBJECTIVE:To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuron...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Klein CJ,Lennon VA,Aston PA,McKeon A,O'Toole O,Quek A,Pittock SJ

    更新日期:2013-02-01 00:00:00

  • Efficacy and Safety of 2 Fingolimod Doses vs Glatiramer Acetate for the Treatment of Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial.

    abstract:Importance:Doses of fingolimod lower than 0.5 mg per day were not investigated during the fingolimod clinical development program. Whether lower doses of fingolimod might retain efficacy with fewer safety risks remains unknown. Objective:To evaluate the efficacy and safety of fingolimod, 0.5 mg, and fingolimod, 0.25 m...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Cree BAC,Goldman MD,Corboy JR,Singer BA,Fox EJ,Arnold DL,Ford C,Weinstock-Guttman B,Bar-Or A,Mientus S,Sienkiewicz D,Zhang Y,Karan R,Tenenbaum N,ASSESS Trial Investigators.

    更新日期:2020-08-24 00:00:00

  • Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project.

    abstract:Importance:Biomarkers do not determine conversion to Alzheimer disease (AD) perfectly, and criteria do not specify how to take patient characteristics into account. Consequently, biomarker use may be challenging for clinicians, especially in patients with mild cognitive impairment (MCI). Objective:To construct biomark...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: van Maurik IS,Zwan MD,Tijms BM,Bouwman FH,Teunissen CE,Scheltens P,Wattjes MP,Barkhof F,Berkhof J,van der Flier WM,Alzheimer’s Disease Neuroimaging Initiative.

    更新日期:2017-12-01 00:00:00

  • Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis.

    abstract:IMPORTANCE:Metabolic syndrome (MetS) is thought to influence several autoimmune diseases, including multiple sclerosis (MS). Anti-inflammatory effects of treatments used for MetS, such as metformin hydrochloride and pioglitazone hydrochloride, have been demonstrated, although clinical evidence supporting use of these t...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Negrotto L,Farez MF,Correale J

    更新日期:2016-05-01 00:00:00

  • JC polyomavirus granule cell neuronopathy in a patient treated with rituximab.

    abstract:IMPORTANCE:Progressive multifocal leukoencephalopathy results from lytic infection of the glia by the JC polyomavirus (JCV); JCV granule cell neuronopathy is caused by infection with a mutated form of JCV, leading to a shift in viral tropism from the glia to cerebellar granule cells. This shift results in a clinical sy...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Dang L,Dang X,Koralnik IJ,Todd PK

    更新日期:2014-04-01 00:00:00

  • Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome: A Randomized Clinical Trial.

    abstract:Importance:Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. Objective:To assess the safety, tolerability, and pharmacodynamics of the microtubule sta...

    journal_title:JAMA neurology

    pub_type: 杂志文章,随机对照试验


    authors: Tsai RM,Miller Z,Koestler M,Rojas JC,Ljubenkov PA,Rosen HJ,Rabinovici GD,Fagan AM,Cobigo Y,Brown JA,Jung JI,Hare E,Geldmacher DS,Natelson-Love M,McKinley EC,Luong PN,Chuu EL,Powers R,Mumford P,Wolf A,Wang P,Sham

    更新日期:2020-02-01 00:00:00

  • Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke: The Save ChildS Study.

    abstract:Importance:Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown. Objective:To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic s...

    journal_title:JAMA neurology

    pub_type: 杂志文章,多中心研究


    authors: Sporns PB,Sträter R,Minnerup J,Wiendl H,Hanning U,Chapot R,Henkes H,Henkes E,Grams A,Dorn F,Nikoubashman O,Wiesmann M,Bier G,Weber A,Broocks G,Fiehler J,Brehm A,Psychogios M,Kaiser D,Yilmaz U,Morotti A,Marik W,

    更新日期:2020-01-01 00:00:00

  • Prevalence of Aging, Dementia, and Multimorbidity in Older Adults With Down Syndrome.

    abstract:Importance:As the life expectancy of people with Down syndrome (DS) has markedly increased over the past decades, older adults with DS may be experiencing a higher incidence of aging conditions. In addition to longevity, the amyloid precursor protein gene located on chromosome 21 places individuals with DS at a high ri...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Bayen E,Possin KL,Chen Y,Cleret de Langavant L,Yaffe K

    更新日期:2018-11-01 00:00:00

  • Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients.

    abstract:IMPORTANCE:Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease. OBJECTIVE:To compare the l...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Groeschel S,Kühl JS,Bley AE,Kehrer C,Weschke B,Döring M,Böhringer J,Schrum J,Santer R,Kohlschütter A,Krägeloh-Mann I,Müller I

    更新日期:2016-09-01 00:00:00

  • Long-term Cognitive Outcomes in Patients With Pediatric-Onset vs Adult-Onset Multiple Sclerosis.

    abstract:Importance:Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term. Objective:To compare long-term information-processing efficiency between...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: McKay KA,Manouchehrinia A,Berrigan L,Fisk JD,Olsson T,Hillert J

    更新日期:2019-06-17 00:00:00

  • Blood pressure and progression of brain atrophy: the SMART-MR Study.

    abstract:IMPORTANCE:Studies have shown that both high and low blood pressure (BP) may play a role in the etiology of brain atrophy. High BP in midlife has been associated with more brain atrophy later in life, whereas studies in older populations have shown a relation between low BP and more brain atrophy. Yet, prospective evid...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Jochemsen HM,Muller M,Visseren FL,Scheltens P,Vincken KL,Mali WP,van der Graaf Y,Geerlings MI,SMART Study Group.

    更新日期:2013-08-01 00:00:00

  • Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

    abstract:IMPORTANCE:Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality. OBJECTIVE:To identify the underlying molecular cause ...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Mirzaa GM,Campbell CD,Solovieff N,Goold C,Jansen LA,Menon S,Timms AE,Conti V,Biag JD,Adams C,Boyle EA,Collins S,Ishak G,Poliachik S,Girisha KM,Yeung KS,Chung BHY,Rahikkala E,Gunter SA,McDaniel SS,Macmurdo CF,Ber

    更新日期:2016-07-01 00:00:00

  • Factors Associated With 8-Year Mortality in Older Patients With Cerebral Small Vessel Disease: The Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study.

    abstract:IMPORTANCE:Gait and cognition have been related to mortality in population-based studies. This association is possibly mediated by cerebral small vessel disease (SVD), which has been associated with mortality as well. It is unknown which factors can predict mortality in individuals with SVD. Identification of high-risk...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: van der Holst HM,van Uden IW,Tuladhar AM,de Laat KF,van Norden AG,Norris DG,van Dijk EJ,Rutten-Jacobs LC,de Leeuw FE

    更新日期:2016-04-01 00:00:00

  • The aging brain and cognition: contribution of vascular injury and aβ to mild cognitive dysfunction.

    abstract:IMPORTANCE:β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate fro...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Marchant NL,Reed BR,Sanossian N,Madison CM,Kriger S,Dhada R,Mack WJ,DeCarli C,Weiner MW,Mungas DM,Chui HC,Jagust WJ

    更新日期:2013-04-01 00:00:00

  • Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial.

    abstract:Importance:Atabecestat, a nonselective oral β-secretase inhibitor, was evaluated in the EARLY trial for slowing cognitive decline in participants with preclinical Alzheimer disease. Preliminary analyses suggested dose-related cognitive worsening and neuropsychiatric adverse events (AEs). Objective:To report efficacy, ...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Sperling R,Henley D,Aisen PS,Raman R,Donohue MC,Ernstrom K,Rafii MS,Streffer J,Shi Y,Karcher K,Raghavan N,Tymofyeyev Y,Bogert J,Brashear HR,Novak G,Thipphawong J,Saad ZS,Kolb H,Rofael H,Sanga P,Romano G

    更新日期:2021-01-19 00:00:00

  • SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy.

    abstract:BACKGROUND:Therapies designed to decrease the level of SOD1 are currently in a clinical trial for patients with superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (ALS). OBJECTIVE:To determine whether the SOD1 protein in cerebral spinal fluid (CSF) may be a pharmacodynamic marker for antisense o...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Winer L,Srinivasan D,Chun S,Lacomis D,Jaffa M,Fagan A,Holtzman DM,Wancewicz E,Bennett CF,Bowser R,Cudkowicz M,Miller TM

    更新日期:2013-02-01 00:00:00

  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

    abstract:Importance:Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been co...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Bridel C,van Wieringen WN,Zetterberg H,Tijms BM,Teunissen CE,and the NFL Group.,Alvarez-Cermeño JC,Andreasson U,Axelsson M,Bäckström DC,Bartos A,Bjerke M,Blennow K,Boxer A,Brundin L,Burman J,Christensen T,Fialová L,Fo

    更新日期:2019-06-17 00:00:00

  • Effect of Smoking Cessation on Multiple Sclerosis Prognosis.

    abstract:IMPORTANCE:Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Ramanujam R,Hedström AK,Manouchehrinia A,Alfredsson L,Olsson T,Bottai M,Hillert J

    更新日期:2015-10-01 00:00:00

  • Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial.

    abstract:Importance:The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown. Objective:To evaluate the differential outcomes of intensive (goal, 110-139 mm Hg) vs standard (goal, 140-17...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Qureshi AI,Huang W,Lobanova I,Barsan WG,Hanley DF,Hsu CY,Lin CL,Silbergleit R,Steiner T,Suarez JI,Toyoda K,Yamamoto H,for ATACH-II trial investigators.

    更新日期:2020-09-08 00:00:00

  • Two Paradigms for Endovascular Thrombectomy After Intravenous Thrombolysis for Acute Ischemic Stroke.

    abstract:Importance:Intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) is recommended to treat acute ischemic stroke (AIS) with a large vessel occlusion (LVO). Most hospitals do not have on-site MT facilities, and most patients need to be transferred secondarily after IVT (drip and ship), which may have an ...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Gerschenfeld G,Muresan IP,Blanc R,Obadia M,Abrivard M,Piotin M,Alamowitch S

    更新日期:2017-05-01 00:00:00

  • Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis: a retrospective analysis of the Get With the Guidelines-Stroke registry.

    abstract:IMPORTANCE:Mild strokes have been poorly represented in thrombolytic trials and only a few series have reported outcomes after treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) after mild stroke. OBJECTIVE:To report treatment complications and short-term outcomes in patients with mild str...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Romano JG,Smith EE,Liang L,Gardener H,Camp S,Shuey L,Cook A,Campo-Bustillo I,Khatri P,Bhatt DL,Fonarow GC,Sacco RL,Schwamm LH

    更新日期:2015-04-01 00:00:00

  • Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

    abstract:Importance:The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective:To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants:During the ZIKV epidem...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Dirlikov E,Major CG,Medina NA,Lugo-Robles R,Matos D,Muñoz-Jordan JL,Colon-Sanchez C,Garcia M,Olivero-Segarra M,Malave G,Rodríguez-Vega GM,Thomas DL,Waterman SH,Sejvar JJ,Luciano CA,Sharp TM,Rivera-García B

    更新日期:2018-09-01 00:00:00

  • Sex and Race Differences in the Association of Incident Ischemic Stroke With Risk Factors.

    abstract:Importance:Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals. Objective:To examine incidence and risk factors for ischemic stroke by sex for black and white individuals. Design, Setting, ...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Howard VJ,Madsen TE,Kleindorfer DO,Judd SE,Rhodes JD,Soliman EZ,Kissela BM,Safford MM,Moy CS,McClure LA,Howard G,Cushman M

    更新日期:2019-02-01 00:00:00