Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
Alzheimers Dement. 2024 Sep;20(9):6423-6440. doi: 10.1002/alz.14139. Epub 2024 Jul 30.
Plasma has been proposed as an alternative to cerebrospinal fluid (CSF) for measuring Alzheimer's disease (AD) biomarkers, but no studies have analyzed in detail which biofluid is more informative for genetics studies of AD.
Eleven proteins associated with AD (α-synuclein, apolipoprotein E [apoE], CLU, GFAP, GRN, NfL, NRGN, SNAP-25, TREM2, VILIP-1, YKL-40) were assessed in plasma (n = 2317) and CSF (n = 3107). Both plasma and CSF genome-wide association study (GWAS) analyses were performed for each protein, followed by functional annotation. Additional characterization for each biomarker included calculation of correlations and predictive power.
Eighteen plasma protein quantitative train loci (pQTLs) associated with 10 proteins and 16 CSF pQTLs associated with 9 proteins were identified. Plasma and CSF shared some genetic loci, but protein levels between tissues correlated weakly. CSF protein levels better associated with AD compared to plasma.
The present results indicate that CSF is more informative than plasma for genetic studies in AD.
The identification of novel protein quantitative trait loci (pQTLs) in both plasma and cerebrospinal fluid (CSF). Plasma and CSF levels of neurodegeneration-related proteins correlated weakly. CSF is more informative than plasma for genetic studies of Alzheimer's disease (AD). Neurofilament light (NfL), triggering receptor expressed on myeloid cells 2 (TREM2), and chitinase-3-like protein 1 (YKL-40) tend to show relatively strong inter-tissue associations. A novel signal in the apolipoprotein E (APOE) region was identified, which is an eQTL for APOC1.
已有研究提出用血浆替代脑脊液（CSF）来测量阿尔茨海默病（AD）的生物标志物，但目前尚无研究详细分析哪种生物体液更有助于 AD 的遗传学研究。
在血浆（n=2317）和脑脊液（n=3107）中评估了 11 种与 AD 相关的蛋白（α-突触核蛋白、载脂蛋白 E [apoE]、CLU、GFAP、GRN、NfL、NRGN、SNAP-25、TREM2、VILIP-1、YKL-40）。对每种蛋白进行了血浆和脑脊液全基因组关联研究（GWAS）分析，并进行了功能注释。对每种生物标志物的额外特征分析包括计算相关性和预测能力。
鉴定出与 10 种蛋白相关的 18 个血浆蛋白定量连锁（pQTL）和与 9 种蛋白相关的 16 个 CSF pQTL。血浆和 CSF 具有一些共同的遗传位点，但组织间蛋白水平相关性较弱。CSF 蛋白水平与 AD 的相关性优于血浆。
本研究结果表明，CSF 比血浆更适合 AD 的遗传研究。
在血浆和脑脊液中均发现了与神经退行性疾病相关蛋白的新型蛋白定量连锁（pQTL）。血浆和 CSF 中神经退行性相关蛋白水平相关性较弱。CSF 比血浆更有助于 AD 的遗传研究。神经丝轻链（NfL）、髓样细胞触发受体 2（TREM2）和几丁质酶-3 样蛋白 1（YKL-40）倾向于表现出较强的组织间相关性。在载脂蛋白 E（APOE）区域鉴定到一个新信号，这是 APOC1 的 eQTL。
