Remote Blood Biomarkers of Longitudinal Cognitive Outcomes in a Population Study.
Remote Blood Biomarkers of Longitudinal Cognitive Outcomes in a Population Study.
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DOI：
10.1002/ana.25874
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发表时间：
2020-12
影响因子：
11.2
通讯作者：
Evans, Denis A.
中科院分区：
文献类型：
--
作者：
Rajan, Kumar B.;Aggarwal, Neelum T.;McAninch, Elizabeth A.;Weuve, Jennifer;Barnes, Lisa L.;Wilson, Robert S.;DeCarli, Charles;Evans, Denis A.
血液生物标志物总tau（t-tau）、神经丝轻蛋白（Nf-L）和胶质细胞酸性蛋白（GFAP）与常见的散发性AD和认知能力下降的纵向相关性尚未确立。使用单分子阵列技术，在1，327名参与者（60%非裔美国人和女性）的人群样本中测量了总tau（t-tau），神经丝光（Nf-L）和胶质细胞酸性蛋白（GFAP）的血清浓度的超灵敏免疫测定，这些参与者进行了AD的临床评估，完成了家庭认知评估，并接受了1.5T结构MRI。较高浓度的血清生物标志物与临床AD的发展相关，尤其是时间特异性相关性显著：t-tau 8-16年，Nf-L和GFAP 4-8年。血清生物标志物与16年内更快的认知下降相关：与最低四分位数相比，基线t-tau高于0.40 pg/mL的下降速度快30%，Nf-L高于25.5 pg/mL的下降速度快110%，GFAP高于232 pg/mL的下降速度快130%。基线GFAP高于232 pg/mL的参与者与低于160 pg/mL的参与者相比，海马体积下降快160%。此外，较高的基线t-tau与第三脑室容积的较快增加相关，并且基线Nf-L和GFAP与皮质厚度的较快下降相关。血清t-tau、Nf-L和GFAP可预测散发性AD和认知能力下降的发展，以及脑结构特征的变化，这表明它们不仅可作为筛选和预测生物标志物，而且可用于捕获阿尔茨海默氏痴呆的发病机制。
The longitudinal association of blood biomarkers of total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic AD and cognitive decline are not established. Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, completed in-home cognitive assessments, and undergone 1.5T structural MRI. Higher concentrations of serum biomarkers were associated with the development of clinical AD, especially, the time-specific associations were notable: t-tau 8–16 years, and Nf-L and GFAP 4–8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years: baseline t-tau above 0.40 pg/mL had 30% faster decline, Nf-L above 25.5 pg/mL had 110% faster decline, and GFAP above 232 pg/mL had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP above 232 pg/mL showed 160% faster decline in hippocampal volume compared to those below 160 pg/mL. Additionally, higher baseline t-tau was associated with faster increase in third ventricular volume, and baseline Nf-L and GFAP were associated with faster decline in cortical thickness. Serum t-tau, Nf-L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer’s dementia.
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影响因子：
3.7
作者：
Dickerson, Bradford C.;Bakkour, Akram;Salat, David H.;Feczko, Eric;Pacheco, Jenni;Greve, Douglas N.;Grodstein, Fran;Wright, Christopher I.;Blacker, Deborah;Rosas, H. Diana;Sperling, Reisa A.;Atri, Alireza;Growdon, John H.;Hyman, Bradley T.;Morris, John C.;Fischl, Bruce;Buckner, Randy L.
通讯作者：
Buckner, Randy L.
DOI：
10.1109/embc.2012.6345882
发表时间：
2012
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
--
作者：
Fletcher E;Carmichael O;Decarli C
通讯作者：
Decarli C
影响因子：
4
作者：
Oeckl, Patrick;Halbgebauer, Steffen;Otto, Markus
通讯作者：
Otto, Markus
影响因子：
14
作者：
Elahi, Fanny M.;Casaletto, Kaitlin B.;Kramer, Joel H.
通讯作者：
Kramer, Joel H.
影响因子：
29
作者：
Mattsson N;Andreasson U;Zetterberg H;Blennow K;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative