Picard Cynthia, Zetterberg Henrik, Blennow Kaj, Villeneuve Sylvia, Poirier Judes
Douglas Mental Health University Institute, Montréal, QC H4H 1R3, Canada.
Centre for the Studies on Prevention of Alzheimer's Disease, Montréal, QC H4H 1R3, Canada.
Genes (Basel). 2025 Jul 12;16(7):818. doi: 10.3390/genes16070818.
SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer's disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers.
Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank.
At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging.
CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition.
丝氨酸蛋白酶抑制剂E1（SERPINE1），也称为纤溶酶原激活物抑制剂（PAI），已被提议作为阿尔茨海默病（AD）早期检测和诊断的潜在血液生物标志物。在先前研究的基础上，本研究将AD患者以及有AD风险者的脑脊液和脑组织中的SERPINE1水平与已确定的AD生物标志物进行了对比。
采用欧联（OLINK）和免疫测定方法，在两个独立队列（PREVENT-AD和ADNI）中对脑脊液SERPINE1蛋白水平进行定量。在另外两个独立队列（加拿大道格拉斯-贝尔脑库和梅奥诊所脑库）中，使用微阵列和RNA测序来测量组织mRNA水平。
在临床前期，脑脊液中磷酸化tau蛋白（pTau）、总tau蛋白（tTau）和突触标志物水平升高，同时海马体积减小，这些与脑脊液SERPINE1水平相关。经尸检确诊的AD患者皮质mRNA水平升高，与区域斑块和缠结密度呈弱相关，但与Braak分期呈强相关。
脑脊液SERPINE1水平可作为检测与AD相关病理变化的早期生物标志物。较高的SERPINE1水平与tau病理的相关性比与淀粉样蛋白形成或沉积的相关性更强。
