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














  • Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease.

    abstract:IMPORTANCE:Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE:To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). ...

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    更新日期:2020-08-10 00:00:00

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    authors: Naasan G,Irani SR,Bettcher BM,Geschwind MD,Gelfand JM

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    abstract:Importance:Apolipoprotein E ε4 (APOEε4) is the single most important genetic risk factor for Alzheimer disease. While APOEε4 is associated with increased amyloid-β burden, its association with cerebral tau pathology has been controversial. Objective:To determine whether APOEε4 is associated with medial temporal tau pa...

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    pub_type: 杂志文章


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    更新日期:2019-06-17 00:00:00

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    pub_type: 杂志文章


    authors: Goldman JS,Quinzii C,Dunning-Broadbent J,Waters C,Mitsumoto H,Brannagan TH 3rd,Cosentino S,Huey ED,Nagy P,Kuo SH

    更新日期:2014-06-01 00:00:00

  • Loss of fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals.

    abstract:IMPORTANCE:Magnetic resonance imaging markers of incipient cognitive decline among healthy elderly individuals have become important for both clarifying the biological underpinnings of dementia and clinically identifying healthy individuals at high risk of cognitive decline. Even though the role of hippocampal atrophy ...

    journal_title:JAMA neurology

    pub_type: 杂志文章


    authors: Fletcher E,Raman M,Huebner P,Liu A,Mungas D,Carmichael O,DeCarli C

    更新日期:2013-11-01 00:00:00

  • Comprehension of an Elevated Amyloid Positron Emission Tomography Biomarker Result by Cognitively Normal Older Adults.

    abstract:Importance:The goal of Alzheimer disease (AD) prevention together with advances in understanding the pathophysiology of AD have led to clinical trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data are needed to inform the processes of describing AD biomarkers to cognitively no...

    journal_title:JAMA neurology

    pub_type: 杂志文章,多中心研究


    authors: Mozersky J,Sankar P,Harkins K,Hachey S,Karlawish J

    更新日期:2018-01-01 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

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    abstract:Importance:The incidence of unprovoked seizures and epilepsy increases considerably in late life, with approximately one-third of seizures being of unknown etiology. While individuals with dementia have a high risk of developing unprovoked seizures, it is unknown whether older adults with late-onset unprovoked seizures...

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    pub_type: 杂志文章


    authors: Keret O,Hoang TD,Xia F,Rosen HJ,Yaffe K

    更新日期:2020-06-01 00:00:00

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    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

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    pub_type: 杂志文章,随机对照试验


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    更新日期:2020-02-01 00:00:00