Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.
Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.
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DOI：
10.1001/jamaneurol.2015.3037
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发表时间：
2016-01
期刊：
影响因子：
29
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Zetterberg H;Skillbäck T;Mattsson N;Trojanowski JQ;Portelius E;Shaw LM;Weiner MW;Blennow K;Alzheimer’s Disease Neuroimaging Initiative
大口径轴突变性在多大程度上有助于阿尔茨海默病（AD）的进展是未知的。脑脊液（CSF）神经丝光（NFL）浓度是大口径有髓轴突损伤的一般标志物。测试CSF NFL浓度是否与AD中的认知下降以及神经变性和白色物质改变的成像证据相关。使用市售免疫测定法分析来自阿尔茨海默病神经成像倡议的AD患者（n = 95）或轻度认知障碍（MCI）患者（n = 192）和认知正常个体（n = 110）的CSF NFL浓度。研究日期为2005年1月至2007年12月。NFL分析于2014年11月进行。在每个诊断组中研究基线CSF NFL浓度与纵向认知障碍、白色物质变化和局部脑萎缩之间的相关性。脑脊液NFL浓度（中位数[四分位距]）在AD痴呆组中较高，（1479 [1134-1842] pg/mL），稳定MCI组（随访期间未进展为AD; 1182 [923-1687] pg/mL），进展性MCI组（MCI在随访期间进展为AD痴呆; 1336 [1061-1693] pg/mL）与对照组受试者相比（1047 [809-1265] pg/mL）（所有P <0.001），AD痴呆组与稳定MCI组相比（P = 0.01）。在MCI组中，通过全脑体积的变化测量，随着时间的推移，较高的CSF NFL浓度与更快的脑萎缩相关（β = −4177，P = .003），心室容积（β = 1835，P < .001），海马体积（β = −54.22，P < .001）;通过简易精神状态检查评分下降反映的疾病进展更快（β =-1.077，P < .001）和阿尔茨海默病评估量表认知子量表评分增加（β = 2.30，P < .001）;和更快的白色物质强度变化（β = 598.7，P < .001）。脑脊液NFL浓度在AD的早期临床阶段增加，并且随着时间的推移与认知恶化和脑结构变化相关。这一发现证实了大口径轴突变性是AD神经变性的重要特征的论点。
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. To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. 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. Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. 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). 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.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
9.9
作者：
Sjögren, M;Rosengren, L;Wallin, A
通讯作者：
Wallin, A
影响因子：
11.2
作者：
Scherling, Carole S.;Hall, Tracey;Berisha, Flora;Klepac, Kristen;Karydas, Anna;Coppola, Giovanni;Kramer, Joel H.;Rabinovici, Gil;Ahlijanian, Michael;Miller, Bruce L.;Seeley, William;Grinberg, Lea T.;Rosen, Howard;Meredith, Jere, Jr.;Boxer, Adam L.
通讯作者：
Boxer, Adam L.
影响因子：
2.8
作者：
Stebbins, G. T.;Murphy, C. M.
通讯作者：
Murphy, C. M.
影响因子：
11.2
作者：
Fortea, Juan;Vilaplana, Eduard;Lleo, Alberto
通讯作者：
Lleo, Alberto