Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, University of Barcelona, Barcelona, Spain.
Atlantic Fellow for Equity in Brain Health, Global Brain Health Institute, University of California, San Francisco, California.
Hum Brain Mapp. 2020 Jun 1;41(8):2004-2013. doi: 10.1002/hbm.24925. Epub 2020 Jan 16.
Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early-onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid-long form of the amyloid-beta protein [Aβ42], total-tau protein [T-tau], neurofilament light chain [NfL], neurogranin [Ng], and 14-3-3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the "AD signature" and "FTLD signature." We tested multiple regression models to find which CSF-biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14-3-3; whereas NfL and 14-3-3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.
先前的研究已经描述了阿尔茨海默病（AD）和额颞叶变性（FTLD）中脑灰质和白质改变的明显模式，以及它们在脑脊液（CSF）生物标志物谱中的差异。我们旨在研究早发性 AD（EOAD）和 FTLD 结构改变与 CSF 生物标志物水平之间的关系。我们纳入了 138 名受试者（64 名 EOAD、26 名 FTLD 和 48 名对照），所有受试者均接受了 3T MRI 脑部扫描和 CSF 生物标志物检测（42 个氨基酸长的淀粉样蛋白-β蛋白 [Aβ42]、总tau 蛋白 [T-tau]、神经丝轻链 [NfL]、神经颗粒蛋白 [Ng]和 14-3-3 水平）。我们使用 FreeSurfer 和 FSL 获得皮质厚度（CTh）和分数各向异性（FA）图。我们研究了 CTh 和 FA 的组间差异，并描述了“AD 特征”和“FTLD 特征”。我们测试了多元回归模型，以确定哪些 CSF 生物标志物能更好地解释每种疾病的神经影像学特征。与 AD 和 FTLD 特征相对应的 CTh 和 FA 图与先前的文献一致。多元回归分析表明，在 AD 特征中能更好地解释 CTh 值的生物标志物是 Aβ 和 14-3-3；而 NfL 和 14-3-3 水平则解释了 FTLD 特征中的 CTh 值。同样，NfL 水平解释了 FTLD 特征中的 FA 值。Ng 水平在任何模型中均无预测作用。生化标志物对 AD 和 FTLD 典型的结构（CTh 和 FA）变化的贡献不同。
