Differential diagnosis of mild cognitive impairment of Alzheimer's disease by Simoa p-tau181 measurements with matching plasma and CSF.
Differential diagnosis of mild cognitive impairment of Alzheimer's disease by Simoa p-tau181 measurements with matching plasma and CSF.
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匹配血浆和脑脊液的SIMOAp-tau181测定鉴别诊断阿尔茨海默病轻度认知损害。
DOI：
10.3389/fnmol.2023.1288930
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发表时间：
2023
影响因子：
4.8
通讯作者：
Xu, Bin
中科院分区：
文献类型：
--
作者：
Wu, Ling;Arvai, Stephanie;Wang, Shih-Hsiu J.;Liu, Andy J.;Xu, Bin
关键词：
阿尔茨海默病（AD）的特征在于长的临床前阶段。虽然晚期AD/痴呆可以通过临床评估、PET成像和已建立的生物流体生物标志物与认知正常个体稳健地区分，但认知正常和轻度认知障碍（MCI）的各种亚型之间的疾病区分仍然是一项具有挑战性的任务。迫切需要可获得的生物流体样品用于早期AD诊断的差异生物标志物。错误折叠的磷酸化tau聚集体（p-tau）存在于称为“tau蛋白病”的多种神经退行性疾病中，其中最常见的是AD。P-tau 181是一种公认的p-tau生物标志物，用于区分AD痴呆和非AD病理。然而，目前尚不清楚p-tau 181是否能够诊断认知正常受试者的早期AD阶段MCI，或者它是否可以区分MCI亚型遗忘型MCI（aMCI）和非遗忘型MCI（naMCI）。在这里，我们评估了p-tau 181在诊断认知正常受试者的MCI和区分aMCI与naMCI亚型中的能力。我们收集了35例认知正常、34例aMCI、17例naMCI和31例AD痴呆病例（共117例受试者）的临床诊断队列的匹配血浆和CSF样本，补充了CSF Aβ42和总tau AD生物标志物水平，并进行了Simoa p-tau 181测定。评价了Simoa p-tau 181检测区分这些队列的诊断能力。我们发现（i）p-tau 181可以稳健地将MCI或aMCI与具有匹配的血浆和CSF样品的认知正常群组区分开，但是这种区分在诊断naMCI与认知正常群组时较弱，（ii）p-tau 181不能将aMCI与naMCI群组区分开，并且（iii）Aβ或总tau负荷的因子显著提高了诊断aMCI与认知正常群组的区分能力。血浆和CSF p-tau 181水平可作为临床前阶段从正常对照诊断aMCI的有前景的生物标志物。但需要更强大的新生物标志物来区分naMCI与认知正常病例或区分MCI亚型，aMCI与naMCI。
Alzheimer’s disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as “tauopathies”, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.
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影响因子：
12.7
作者：
Ashton NJ;Pascoal TA;Karikari TK;Benedet AL;Lantero-Rodriguez J;Brinkmalm G;Snellman A;Schöll M;Troakes C;Hye A;Gauthier S;Vanmechelen E;Zetterberg H;Rosa-Neto P;Blennow K
通讯作者：
Blennow K
DOI：
10.1016/s1474-4422(21)00214-3
发表时间：
2021-09
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Thijssen EH;La Joie R;Strom A;Fonseca C;Iaccarino L;Wolf A;Spina S;Allen IE;Cobigo Y;Heuer H;VandeVrede L;Proctor NK;Lago AL;Baker S;Sivasankaran R;Kieloch A;Kinhikar A;Yu L;Valentin MA;Jeromin A;Zetterberg H;Hansson O;Mattsson-Carlgren N;Graham D;Blennow K;Kramer JH;Grinberg LT;Seeley WW;Rosen H;Boeve BF;Miller BL;Teunissen CE;Rabinovici GD;Rojas JC;Dage JL;Boxer AL;Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators
通讯作者：
Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators
DOI：
10.1016/j.jalz.2014.02.004
发表时间：
2015-01
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Blennow K;Dubois B;Fagan AM;Lewczuk P;de Leon MJ;Hampel H
通讯作者：
Hampel H
影响因子：
14
作者：
Vermunt, Lisa;Sikkes, Sietske A. M.;Coley, N.
通讯作者：
Coley, N.
影响因子：
8.8
作者：
Salvadores, Natalia;Shahnawaz, Mohammad;Soto, Claudio
通讯作者：
Soto, Claudio