Göschel Laura, Dell'Orco Andrea, Fillmer Ariane, Aydin Semiha, Ittermann Bernd, Riemann Layla, Lehmann Sylvain, Cano Stefan, Melin Jeanette, Pendrill Leslie, Hoede Patty L, Teunissen Charlotte E, Schwarz Claudia, Grittner Ulrike, Körtvélyessy Péter, Flöel Agnes
Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Neuroscience Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Alzheimers Dement. 2024 Dec;20(12):8684-8699. doi: 10.1002/alz.14318. Epub 2024 Nov 19.
Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)-derived measurements in Alzheimer's disease (AD) remain unclear.
In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and 7T structural and functional MR imaging and spectroscopy using linear mixed models.
Increases in both p-tau181 and GFAP showed the strongest associations to 7T MR-derived measurements, particularly with decreasing parietal cortical thickness, decreasing connectivity of the salience network, and increasing neuroinflammation as determined by MR spectroscopy (MRS) myo-inositol.
Both plasma p-tau181 and GFAP appear to reflect disease progression, as indicated by 7T MR-derived brain changes which are not limited to areas known to be affected by tau pathology and neuroinflammation measured by MRS myo-inositol, respectively.
This study leverages high-resolution 7T magnetic resonance (MR) imaging and MR spectroscopy (MRS) for Alzheimer's disease (AD) plasma biomarker insights. Tau phosphorylated at threonine 181 (p-tau181) and glial fibrillary acidic protein (GFAP) showed the largest changes over time, particularly in the AD group. p-tau181 and GFAP are robust in reflecting 7T MR-based changes in AD. The strongest associations were for frontal/parietal MR changes and MRS neuroinflammation.
血浆生物标志物的纵向变化与阿尔茨海默病（AD）中脑磁共振（MR）衍生测量值之间的关联仍不清楚。
在一个由健康老年人和AD连续体患者组成的研究人群（n = 127）中，我们使用线性混合模型研究了纵向血浆淀粉样β42/40比率、苏氨酸181磷酸化的tau（p-tau181）、胶质纤维酸性蛋白（GFAP）、神经丝轻链（NfL）与7T结构和功能MR成像及波谱之间的关联。
p-tau181和GFAP的增加与7T MR衍生测量值的关联最强，特别是与顶叶皮质厚度减小、突显网络连通性降低以及磁共振波谱（MRS）肌醇测定的神经炎症增加有关。
血浆p-tau181和GFAP似乎都反映了疾病进展，7T MR衍生的脑变化表明了这一点，这些变化不限于分别由MRS肌醇测量的已知受tau病理和神经炎症影响的区域。
本研究利用高分辨率7T磁共振（MR）成像和磁共振波谱（MRS）来深入了解AD的血浆生物标志物。苏氨酸181磷酸化的tau（p-tau181）和胶质纤维酸性蛋白（GFAP）随时间变化最大，尤其是在AD组。p-tau181和GFAP在反映AD中基于7T MR的变化方面表现稳健。最强的关联是额叶/顶叶MR变化和MRS神经炎症。
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