Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease.
Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease.
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DOI：
10.1038/s41398-020-01137-1
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发表时间：
2021-01-11
影响因子：
6.8
通讯作者：
Martins RN
中科院分区：
文献类型：
--
作者：
Chatterjee P;Pedrini S;Stoops E;Goozee K;Villemagne VL;Asih PR;Verberk IMW;Dave P;Taddei K;Sohrabi HR;Zetterberg H;Blennow K;Teunissen CE;Vanderstichele HM;Martins RN
胶质纤维酸性蛋白(GFAP)是一种星形细胞骨架蛋白，可在血液样本中检测到，并与阿尔茨海默病(AD)有关。然而，基于脑淀粉样蛋白(Aβ，Aβ)负荷，尚未对认知正常、有AD风险的老年人的血浆胶质纤维酸性蛋白进行研究。通过Aβ正电子发射断层扫描对低(A = ，nβ63)和高(A = +，nβ33)脑Aβ负荷的参与者(65-90岁)的血浆胶质纤维酸性蛋白和血浆Aβ1-42/A = 1-40比率进行横断面分析。用单分子阵列(SIMOA)平台测定血浆胶质纤维酸性蛋白、Aβ1-42、Aβ1-40。在调整了年龄、性别和载脂蛋白E- 4携带量后，A +参与者的血浆胶质纤维酸性蛋白水平显著高于Aβ参与者(pβ<； 0.00001)，而血浆A 1-42/Aβ1-40比值显著低于Aβ−参与者(p <； 0.005)。基于相同协变量Logistic回归的受试者工作特征曲线，即基础模型，区分了Aβ+和Aβ−(曲线下面积，AUC = 0.78)，但在基础模型(AUC = 0.91)中加入血浆GFAP后表现更好，并进一步改善了血浆Aβ1-42/Aβ1-40比率(AUC = 0.92)。目前的研究结果表明，认知正常的老年AD患者血浆GFAP水平升高。这些观察表明，星形胶质细胞的损伤或激活始于AD的症状前阶段，并与脑Aβ负荷有关。从本研究中观察到，血浆胶质纤维酸性蛋白可能有助于诊断患有AD的认知正常老年人的血液生物标志物(连同血浆Aβ1-42/Aβ1-40比值)。
Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
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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：
4
作者：
Chatterjee, Pratishtha;Elmi, Mitra;Martins, Ralph N.
通讯作者：
Martins, Ralph N.
影响因子：
11
作者：
Goozee, K.;Chatterjee, P.;Martins, R. N.
通讯作者：
Martins, R. N.
影响因子：
9.3
作者：
Carter, Stephen F.;Scholl, Michael;Nordberg, Agneta
通讯作者：
Nordberg, Agneta
影响因子：
4
作者：
Chatterjee, Pratishtha;Goozee, Kathryn;Martins, Ralph N.
通讯作者：
Martins, Ralph N.