Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease.
Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease.
复制标题
常染色体主导的阿尔茨海默氏病中CSF生物标志物的纵向变化。
DOI：
10.1126/scitranslmed.3007901
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发表时间：
2014-03-05
影响因子：
17.1
通讯作者：
Dominantly Inherited Alzheimer Network
中科院分区：
文献类型：
--
作者：
Fagan AM;Xiong C;Jasielec MS;Bateman RJ;Goate AM;Benzinger TL;Ghetti B;Martins RN;Masters CL;Mayeux R;Ringman JM;Rossor MN;Salloway S;Schofield PR;Sperling RA;Marcus D;Cairns NJ;Buckles VD;Ladenson JH;Morris JC;Holtzman DM;Dominantly Inherited Alzheimer Network
临床病理学证据表明阿尔茨海默病（AD）的病理学在认知症状之前多年就开始了。需要生物标志物来识别在此无症状（“临床前”）阶段期间受影响的个体，以允许用旨在保护正常脑功能的潜在疾病修饰疗法进行干预。常染色体显性AD（ADAD）突变家族的研究提供了一个独特的和强大的手段来调查AD生物标志物的变化在无症状期间。在这项比较脑脊液（CSF）、血浆和体内淀粉样蛋白成像的生物标志物研究中，在入选显性遗传性阿尔茨海默病网络（DIAN）的ADAD家族个体中基线时获得的横断面数据表明，CSF淀粉样蛋白-β1-42（Aβ1-42）浓度降低与β-淀粉样蛋白斑块的存在相关，CSF tau、ptau 181和VILIP-1浓度升高，无症状突变携带者在症状发作时估计年龄（EAO）之前10-20年以及检测到认知缺陷之前，存在神经原纤维缠结和/或神经元损伤/死亡的标志物。然而，当纵向比较时，个体内神经元损伤/死亡的CSF生物标志物的浓度在其EAO后降低，表明急性神经退行性过程与症状性疾病进展减缓。这些结果强调了在对疾病过程中的生物标志物轨迹进行建模时，纵向的人内评估的重要性。如果得到证实，这种模式可能会影响临床试验中阳性神经退行性生物标志物结局的定义。
Clinicopathologic evidence suggests the pathology of Alzheimer disease (AD) begins many years prior to cognitive symptoms. Biomarkers are required to identify affected individuals during this asymptomatic (“pre-clinical”) stage to permit intervention with potential disease-modifying therapies designed to preserve normal brain function. Studies of families with autosomal-dominant AD (ADAD) mutations provide a unique and powerful means to investigate AD biomarker changes during the asymptomatic period. In this biomarker study comparing cerebrospinal fluid (CSF), plasma and in vivo amyloid imaging, cross-sectional data obtained at baseline in individuals from ADAD families enrolled in the Dominantly Inherited Alzheimer Network (DIAN) demonstrate reduced concentrations of CSF amyloid-β1-42 (Aβ1–42) associated with the presence of β-amyloid plaques, and elevated concentrations of CSF tau, ptau181 and VILIP-1, markers of neurofibrillary tangles and/or neuronal injury/death, in asymptomatic mutation carriers 10-20 years prior to their estimated age at symptom onset (EAO), and prior to detection of cognitive deficits. When compared longitudinally, however, the concentrations of CSF biomarkers of neuronal injury/death within-individuals decrease after their EAO, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression. These results emphasize the importance of longitudinal, within-person assessment when modeling biomarker trajectories across the course of the disease. If corroborated, this pattern may influence the definition of a positive neurodegenerative biomarker outcome in clinical trials.
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影响因子：
4.2
作者：
Bouwman, Femke H.;Schoonenboom, Niki S. M.;van der Flier, Wiesje M.
通讯作者：
van der Flier, Wiesje M.
影响因子：
11.1
作者：
Fagan, Anne M.;Mintun, Mark A.;Shah, Aarti R.;Aldea, Patricia;Roe, Catherine M.;Mach, Robert H.;Marcus, Daniel;Morris, John C.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
4.2
作者：
Forsberg, Anton;Engler, Henry;Nordberg, Agneta
通讯作者：
Nordberg, Agneta
影响因子：
2.5
作者：
Blomberg, M;Jensen, M;Wahlund, LO
通讯作者：
Wahlund, LO
影响因子：
2.4
作者：
Englund, Hillevi;Anneren, Goran;Hoglund, Kina
通讯作者：
Hoglund, Kina