Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease.
Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease.
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DOI：
10.1002/emmm.200900048
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发表时间：
2009-11
影响因子：
11.1
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Fagan, Anne M.;Mintun, Mark A.;Shah, Aarti R.;Aldea, Patricia;Roe, Catherine M.;Mach, Robert H.;Marcus, Daniel;Morris, John C.;Holtzman, David M.
据估计，阿尔茨海默氏病 (AD) 的病理学在可检测到的认知能力下降之前许多年就已经发生。液体和成像生物标志物可以识别处于早期症状甚至临床前阶段的人，可能此时潜在的治疗方法可以最好地保留认知功能。我们之前报道过，脑脊液 (CSF) 中的淀粉样蛋白-β42 (Aβ42) 水平是通过淀粉样蛋白示踪剂匹兹堡化合物 B (PIB) 检测到的脑淀粉样蛋白的极好标志物。利用 189 名认知正常参与者的数据，我们现在报告了 CSF tau/ptau181（神经原纤维缠结的主要成分）与皮质淀粉样蛋白数量之间的正线性关系。我们观察到皮质 PIB 与 CSF Aβ42 的结合存在很强的负相关关系，但与血浆 Aβ 种类无关。有些个体的 CSF Aβ42 较低，但没有皮质 PIB 结合。总之，这些数据表明，大脑 Aβ42 代谢和淀粉样蛋白形成的变化是 AD 的早期致病事件，并且 CSF tau 代谢的显着破坏可能发生在 Aβ42 最初聚集并随着淀粉样蛋白积累而增加之后。这些发现对临床前 AD 诊断和治疗具有重要意义。
Alzheimer's disease (AD) pathology is estimated to develop many years before detectable cognitive decline. Fluid and imaging biomarkers may identify people in early symptomatic and even preclinical stages, possibly when potential treatments can best preserve cognitive function. We previously reported that cerebrospinal fluid (CSF) levels of amyloid-β42 (Aβ42) serve as an excellent marker for brain amyloid as detected by the amyloid tracer, Pittsburgh compound B (PIB). Using data from 189 cognitively normal participants, we now report a positive linear relationship between CSF tau/ptau181 (primary constituents of neurofibrillary tangles) with the amount of cortical amyloid. We observe a strong inverse relationship of cortical PIB binding with CSF Aβ42 but not for plasma Aβ species. Some individuals have low CSF Aβ42 but no cortical PIB binding. Together, these data suggest that changes in brain Aβ42 metabolism and amyloid formation are early pathogenic events in AD, and that significant disruptions in CSF tau metabolism likely occur after Aβ42 initially aggregates and increases as amyloid accumulates. These findings have important implications for preclinical AD diagnosis and treatment.
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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.
影响因子：
9.9
作者：
Li, G.;Sokal, I.;Montine, T. J.
通讯作者：
Montine, T. J.
影响因子：
11.2
作者：
Klunk, WE;Engler, H;Långström, B
通讯作者：
Långström, B
影响因子：
--
作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
通讯作者：
Klunk, William E.
影响因子：
--
作者：
Fukumoto, H;Tennis, M;Irizarry, MC
通讯作者：
Irizarry, MC