Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients.
Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients.
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结合血浆磷酸化tau蛋白和可获得的措施来评估轻度认知障碍患者向阿尔茨海默氏痴呆的进展
DOI：
10.1186/s13195-022-00990-0
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发表时间：
2022-03-29
期刊：
影响因子：
--
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Pichet Binette A;Palmqvist S;Bali D;Farrar G;Buckley CJ;Wolk DA;Zetterberg H;Blennow K;Janelidze S;Hansson O
到目前为止，还没有临床可用的微创生物标志物来准确识别轻度认知障碍（MCI）患者，这些患者更有可能发展为阿尔茨海默病（AD）痴呆。最近血液标记物的出现为更容易获得的生物标记物打开了大门。我们的目的是确定哪些与AD相关的血浆生物标志物和其他容易获得的评估组合可以最好地预测轻度认知障碍（MCI）患者AD痴呆的进展。我们纳入了失忆性轻度认知损伤患者（n = 110），前瞻性随访3年以评估临床状况。基线血浆生物标志物（淀粉样蛋白-β 42/40，磷酸化tau217 [p-tau217]，神经丝光和胶质纤维酸性蛋白），海马体积，APOE基因型和认知测试可用。以3年内转化为淀粉样蛋白阳性AD痴呆为结局的Logistic回归用于评估基线时测量的不同生物标志物的性能，单独使用或联合使用。第一次分析仅包括血浆生物标志物，以确定与阿尔茨海默病痴呆转化最相关的生物标志物。其次，将海马体积、APOE基因型和简短认知综合评分（mPACC）与最佳血浆生物标志物相结合。在所有血浆生物标志物组合中，p-tau217单独与所有其他组合相比，在区分AD痴呆进展方面表现最佳（AUC 0.84, 95% CI 0.75-0.93）。接下来，将p-tau217与海马体积、认知和APOE基因型结合，可以在MCI进展者与非进展者之间提供最佳的区分（AUC为0.89,0.82-0.95）。在结合不同标记的几个最佳模型中，p-tau217和认知一直是主要的贡献者。包含p-tau217和认知的最精简模型具有相似的模型拟合，但AUC略低（0.87,0.79 ~ 0.95,p = 0.07）。我们发现，结合血浆p-tau217和简短的认知综合评分与MCI患者进展为AD痴呆的高风险密切相关，这表明这些指标可能是未来早期AD预后算法的关键组成部分。NCT01028053, 2009年12月9日注册。
Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer’s disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75–0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82–0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79–0.95, p = 0.07). We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD. NCT01028053, registered December 9, 2009.
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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：
6.8
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
通讯作者：
Martins RN
DOI：
10.1186/s13195-021-00804-9
发表时间：
2021-03-27
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Cicognola C;Janelidze S;Hertze J;Zetterberg H;Blennow K;Mattsson-Carlgren N;Hansson O
通讯作者：
Hansson O
影响因子：
11.1
作者：
Mattsson-Carlgren N;Janelidze S;Bateman RJ;Smith R;Stomrud E;Serrano GE;Reiman EM;Palmqvist S;Dage JL;Beach TG;Hansson O
通讯作者：
Hansson O
DOI：
10.1186/s13195-017-0301-7
发表时间：
2017-10-10
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Frölich L;Peters O;Lewczuk P;Gruber O;Teipel SJ;Gertz HJ;Jahn H;Jessen F;Kurz A;Luckhaus C;Hüll M;Pantel J;Reischies FM;Schröder J;Wagner M;Rienhoff O;Wolf S;Bauer C;Schuchhardt J;Heuser I;Rüther E;Henn F;Maier W;Wiltfang J;Kornhuber J
通讯作者：
Kornhuber J