Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
J Alzheimers Dis. 2017;58(4):1245-1254. doi: 10.3233/JAD-161114.
Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study.
Determine the neuroanatomical correlates of plasma tau using voxel-based analysis.
Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOEɛ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ+) if CSF Aβ42 was <192 pg/mL.
Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus.
Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ+ participants and not Aβ-participants.
与前驱期和对照相比，阿尔茨海默病（AD）患者外周（血浆）和中枢（脑脊液，CSF）tau 水平更高。虽然已经证明 CSF tau 浓度升高与 AD 特异性区域的灰质密度（GMD）降低相关，但尚未在大型研究中检查血浆中的这种相关性。
使用基于体素的分析确定血浆 tau 的神经解剖学相关性。
收集了 508 名 ADNI 参与者的横断面数据，用于临床、血浆总 tau（t-tau）、CSF 淀粉样蛋白（Aβ42）和 tau 以及 MRI 变量。使用回归模型在体素基础上评估血浆 tau 与 GMD 之间以及 CSF t-tau 与 GMD 之间的关系。年龄、性别、APOEɛ4 状态、诊断和总颅内体积在适当情况下用作协变量。如果 CSF Aβ42<192 pg/mL，则将参与者定义为淀粉样蛋白阳性（Aβ+）。
血浆 tau 与内侧颞叶（MTL）、楔前叶、丘脑和纹状体的 GMD 呈负相关。与丘脑和纹状体的关联独立于诊断。在 MTL、楔前叶和额叶的 Aβ+参与者中，血浆 tau 与 GMD 之间也存在负相关。与 CSF t-tau 相比，血浆 tau 显示出明显不同的相关脑萎缩模式，仅在梭状回有小的重叠区域。
血浆 tau 可能是神经退行性变的非特异性标志物，但考虑到低 GMD 与 Aβ+参与者的血浆 tau 相关，而与 Aβ-参与者无关，因此仍然与 AD 相关。
