Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Alzheimers Res Ther. 2023 Sep 22;15(1):157. doi: 10.1186/s13195-023-01302-w.
Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.
We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (C-PIB), tau-PET (F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).
Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model.
Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.
血浆磷酸化 tau（p-tau）已成为阿尔茨海默病（AD）的有前途的生物标志物。研究报告称，p-tau 与 tau-PET 之间存在很强的关联，主要是由淀粉样蛋白阳性和淀粉样蛋白阴性患者之间的差异驱动的。然而，在具有支持 AD 生物标志物诊断的认知障碍患者中，p-tau 与 tau-PET 之间的关系特征较少。我们在 AD 的临床阶段患者中对血浆 p-tau217 和 tau-PET 进行了直接比较，并进一步评估了它们与人口统计学、临床和生物标志物变量的关系。
我们回顾性纳入了 87 名淀粉样蛋白阳性的患者，这些患者因 AD 导致 MCI 或痴呆，他们在 1 年内接受了结构 MRI、淀粉样蛋白-PET（C-PIB）、tau-PET（F-flortaucipir，FTP）和血液采集评估（年龄=66±10，48%为女性）。用 Centiloids（CL）对淀粉样蛋白-PET 进行量化，并用参照小脑下皮层的标准化摄取比值（SUVR）来测量皮质 tau-PET 结合。使用 Meso Scale Discovery 平台上基于电化学发光的测定法测量血浆 p-tau217 浓度。使用 FreeSurfer 对 MRI 衍生的皮质体积进行量化。在基线（n=85）和随访（n=28；1.5±0.7 年）时可获得简易精神状态检查（MMSE）评分。
血浆 p-tau217 和皮质 FTP-SUVR 相关（r=0.61，p<0.001），尤其是在颞顶叶和背外侧额叶皮质中。较高的 p-tau217 和 FTP-SUVR 值与较年轻的年龄、女性和较低的皮质体积相关，但与 APOE-ε4 携带状态无关。PIB-PET Centiloids 与 FTP-SUVR 弱相关（r=0.26，p=0.02），但与 p-tau217 无关（r=0.10，p=0.36）。PET-血浆的区域相关性因淀粉样蛋白负担而异，在中等淀粉样蛋白 PET 负担的患者中，p-tau217 与 tau-PET 的相关性更强，在高淀粉样蛋白 PET 负担的患者中，p-tau217 与主要皮质的 tau-PET 相关性更强。较高的 p-tau217 和 FTP-SUVR 值与横截面 MMSE 评分较低独立相关，而仅在基线时将两者纳入同一模型时，FTP-SUVR 才可预测纵向 MMSE 下降。
在淀粉样蛋白 PET 阳性的 MCI 或因 AD 导致的痴呆患者中，血浆 p-tau217 和 tau-PET 强烈相关，并且它们与人口统计学变量和下游神经退行性变标志物的相关性具有相似的模式。
