Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer's disease.
Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer's disease.
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DOI：
10.1186/s13195-017-0335-x
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发表时间：
2018-01-15
期刊：
影响因子：
--
通讯作者：
Blennow K
中科院分区：
文献类型：
--
作者：
Duits FH;Brinkmalm G;Teunissen CE;Brinkmalm A;Scheltens P;Van der Flier WM;Zetterberg H;Blennow K
我们研究了一组由参与突触功能和免疫的蛋白质组成的12种潜在的新型生物标志物是否能够区分阿尔茨海默病（AD）患者和轻度认知障碍（MCI）患者与对照组。我们纳入了来自阿姆斯特丹痴呆队列的40名对照受试者、40名MCI受试者和40名AD受试者，这些受试者的年龄和性别匹配（年龄65 ± 5岁，19名[48%]女性）。MCI患者的平均随访时间为3年。使用平行反应监测质谱法分析脑脊液中每种蛋白质的两种或三种胰蛋白酶肽。加入相应的稳定同位素标记的肽并用作参比肽。使用多水平广义估计方程（GEE），每个受试者和每个蛋白质（作为受试者内变量）的肽聚类，以评估诊断组之间的差异。为了评估单个蛋白质的差异效应，我们在模型中包括诊断×蛋白质相互作用。进行单独的GEE分析，以评估稳定患者和进展性MCI（MCI-AD）患者之间的差异。诊断有主效应（p < 0.01），诊断和蛋白质之间有相互作用（p < 0.01）。根据蛋白质分层的分析显示，MCI患者的大多数蛋白质水平较高，尤其是MCI-AD患者。嗜铬粒蛋白A、分泌粒蛋白II、neurexin 3和neuropentraxin 1显示出最大的效应量; MCI患者与对照受试者或AD患者的β值范围为0.53至0.78，MCI-AD患者与稳定MCI患者的β值范围为0.67至0.98。相比之下，AD患者的神经分泌蛋白VGF低于MCI患者（ε =-0.93 [SE 0.22]）和对照受试者（ε = 0.46 [SE 0.19]）。我们的研究结果表明，参与囊泡转运和突触稳定性的几种蛋白质在MCI患者中升高，特别是在MCI进展为AD痴呆的患者中。这可能反映了AD病理生理级联反应的早期事件。这些蛋白质可作为疾病阶段或疾病早期症状阶段的预后标志物。本文的在线版本（10.1186/s13195-017-0335-x）包含补充材料，可供授权用户使用。
We investigated whether a panel of 12 potential novel biomarkers consisting of proteins involved in synapse functioning and immunity would be able to distinguish patients with Alzheimer’s disease (AD) and patients with mild cognitive impairment (MCI) from control subjects. We included 40 control subjects, 40 subjects with MCI, and 40 subjects with AD from the Amsterdam Dementia Cohort who were matched for age and sex (age 65 ± 5 years, 19 [48%] women). The mean follow-up of patients with MCI was 3 years. Two or three tryptic peptides per protein were analyzed in cerebrospinal fluid using parallel reaction monitoring mass spectrometry. Corresponding stable isotope-labeled peptides were added and used as reference peptides. Multilevel generalized estimating equations (GEEs) with peptides clustered per subject and per protein (as within-subject variables) were used to assess differences between diagnostic groups. To assess differential effects of individual proteins, we included the diagnosis × protein interaction in the model. Separate GEE analyses were performed to assess differences between stable patients and patients with progressive MCI (MCI-AD). There was a main effect for diagnosis (p < 0.01) and an interaction between diagnosis and protein (p < 0.01). Analysis stratified according to protein showed higher levels in patients with MCI for most proteins, especially in patients with MCI-AD. Chromogranin A, secretogranin II, neurexin 3, and neuropentraxin 1 showed the largest effect sizes; β values ranged from 0.53 to 0.78 for patients with MCI versus control subjects or patients with AD, and from 0.67 to 0.98 for patients with MCI-AD versus patients with stable MCI. In contrast, neurosecretory protein VGF was lower in patients with AD than in patients with MCI (ß = −0.93 [SE 0.22]) and control subjects (ß = 0.46 [SE 0.19]). Our results suggest that several proteins involved in vesicular transport and synaptic stability are elevated in patients with MCI, especially in patients with MCI progressing to AD dementia. This may reflect early events in the AD pathophysiological cascade. These proteins may be valuable as disease stage or prognostic markers in an early symptomatic stage of the disease. The online version of this article (10.1186/s13195-017-0335-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Jahn H;Wittke S;Zürbig P;Raedler TJ;Arlt S;Kellmann M;Mullen W;Eichenlaub M;Mischak H;Wiedemann K
通讯作者：
Wiedemann K
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
DOI：
10.1523/jneurosci.3145-08.2008
发表时间：
2008-09-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bozdagi O;Rich E;Tronel S;Sadahiro M;Patterson K;Shapiro ML;Alberini CM;Huntley GW;Salton SR
通讯作者：
Salton SR
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
3.1
作者：
Marksteiner, J;Kaufmann, WA;Humpel, C
通讯作者：
Humpel, C