Montoliu-Gaya Laia, Valeriano-Lorenzo Elizabeth, Ashton Nicholas J, López-González Francisco J, Lantero-Rodriguez Juan, Ruiz-González Alicia, Pastor Ana Belén, Frades Belen, Zea-Sevilla María Ascensión, Valentí Meritxell, Ruiz-Valderrey Paloma, Saiz Laura, Burgueño-García Iván, López-Martínez Maria José, Del Ser Teodoro, Brinkmalm Gunnar, Zetterberg Henrik, Rábano Alberto, Gobom Johan, Blennow Kaj, Sánchez-Juan Pascual
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Reina Sofia Foundation Alzheimer Center, CIEN Foundation, ISCIII, Madrid, Spain.
Alzheimers Dement. 2025 Aug;21(8):e70562. doi: 10.1002/alz.70562.
Plasma-to-autopsy studies are essential to understand how tau blood biomarkers change in relation to Alzheimer's disease (AD) brain pathology and how they are influenced by brain co-pathologies and comorbidities.
Plasma samples from 102 brain donors of the Vallecas Alzheimer Reina Sofia cohort were analyzed using a mass spectrometry method to measure the levels of six phosphorylated and two non-phosphorylated tau biomarkers.
In cases with high pathological burden of AD, phosphorylated tau (p-tau)217 showed associations with neurofibrillary tangle counts across all regions, while p-tau205 was primarily linked to the frontal cortex, and the non-phosphorylated tau peptides were linked to the temporal cortex. Plasma tau levels decreased as Lewy body pathology progressed, even among individuals at the same tau Braak stage. All plasma biomarkers correlated with creatinine levels, as a marker of renal dysfunction, but this effect was mitigated when using the ratios phospho/non-phospho.
Understanding how plasma tau biomarkers are influenced by co-pathologies and comorbidities is crucial for their accurate implementation.
The plasma phosphorylated tau (p-tau)217 ratio, followed by the p-tau205 ratio and p-tau217, were the best-performing biomarkers for detecting neuropathologically confirmed Alzheimer's disease (AD). In high AD cases, p-tau217 showed associations with neurofibrillary tangle (NFT) counts across all regions, while p-tau205 was primarily linked to the frontal cortex, and non-phosphorylated tau peptides were linked to the temporal cortex. We observed a decline in plasma tau levels as Lewy body pathology progressed, even among individuals at the same tau Braak stage. All plasma biomarkers correlated with creatinine levels, as a marker of renal dysfunction, but this effect was mitigated when using the ratios. Plasma p-tau199 displayed a distinct behavior compared to other p-tau species, showing no association with NFT counts in any brain region, but demonstrating significant correlations with brain volume and an effect on survival time.
血浆与尸检研究对于理解tau血液生物标志物如何随阿尔茨海默病（AD）脑病理学变化以及它们如何受到脑共病和合并症的影响至关重要。
使用质谱法分析了来自巴列卡斯阿尔茨海默雷纳索菲亚队列的102名脑捐赠者的血浆样本，以测量六种磷酸化和两种非磷酸化tau生物标志物的水平。
在AD病理负担较高的病例中，磷酸化tau（p-tau）217在所有区域均与神经原纤维缠结计数相关，而p-tau205主要与额叶皮质相关，非磷酸化tau肽与颞叶皮质相关。随着路易体病理进展，血浆tau水平下降，即使在处于相同tau Braak阶段的个体中也是如此。所有血浆生物标志物均与作为肾功能不全标志物的肌酐水平相关，但使用磷酸化/非磷酸化比率时这种影响会减轻。
了解血浆tau生物标志物如何受到共病和合并症的影响对于其准确应用至关重要。
血浆磷酸化tau（p-tau）217比率，其次是p-tau205比率和p-tau217，是检测经神经病理学证实的阿尔茨海默病（AD）的最佳生物标志物。在高AD病例中，p-tau217在所有区域均与神经原纤维缠结（NFT）计数相关，而p-tau205主要与额叶皮质相关，非磷酸化tau肽与颞叶皮质相关。我们观察到随着路易体病理进展，血浆tau水平下降，即使在处于相同tau Braak阶段的个体中也是如此。所有血浆生物标志物均与作为肾功能不全标志物的肌酐水平相关，但使用比率时这种影响会减轻。与其他p-tau种类相比，血浆p-tau199表现出独特的行为，在任何脑区均与NFT计数无关，但与脑体积显著相关并对生存时间有影响。
