Berry Kacey, Asken Breton M, Grab Joshua D, Chan Brandon, Lario Lago Argentina, Wong Randi, Seetharaman Srilakshmi, LaHue Sara C, Possin Katherine L, Rojas Julio C, Kramer Joel H, Boxer Adam L, Lai Jennifer C, VandeVrede Lawren
Department of Medicine Division of Gastroenterology University of California San Francisco California USA.
Weill Institute for Neurosciences Department of Neurology Memory and Aging Center University of California San Francisco California USA.
Alzheimers Dement (Amst). 2022 Jul 12;14(1):e12321. doi: 10.1002/dad2.12321. eCollection 2022.
The impact of hepatorenal function on plasma biomarkers of neuropathology is unknown. Herein, we measured several plasma biomarkers in patients with cirrhosis.
Plasma phosphorylated tau (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-tau), and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) were measured in 135 adults with cirrhosis and 22 healthy controls using Simoa. Within cirrhosis, associations between biomarkers and hepatorenal function were explored using linear regression.
p-tau181, NfL, t-tau, and UCHL1 were increased 2- to 4-fold in cirrhosis, whereas GFAP was not increased. Within cirrhosis, creatinine moderately correlated with p-tau181 ( = 0.75, < .01), NfL ( = 0.32, < .01), and t-tau ( = 0.31, < .01), but not GFAP ( = -0.01, = .88) or UCHL1 ( = -0.05, = .60), whereas albumin showed weak, inverse correlations: p-tau181 ( = -0.18, < .01), NfL ( = -0.22, < .01), GFAP ( = -0.17, < .05), t-tau ( = -0.20, = .02), and UCHL1 ( = -0.15, = .09).
Elevated p-tau181, NfL, and t-tau in cirrhosis were associated with renal impairment and hypoalbuminemia, suggesting that hepatorenal function may be important when interpreting plasma biomarkers of neuropathology.
肝肾功对神经病理学血浆生物标志物的影响尚不清楚。在此，我们检测了肝硬化患者的几种血浆生物标志物。
使用Simoa检测了135例肝硬化成人患者和22例健康对照者的血浆磷酸化tau蛋白（p-tau181）、神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）、总tau蛋白（t-tau）和泛素羧基末端水解酶L1（UCHL1）。在肝硬化患者中，采用线性回归分析生物标志物与肝肾功之间的关联。
肝硬化患者的p-tau181、NfL、t-tau和UCHL1升高了2至4倍，而GFAP未升高。在肝硬化患者中，肌酐与p-tau181（r = 0.75，P <.01）、NfL（r = 0.32，P <.01）和t-tau（r = 0.31，P <.01）中度相关，但与GFAP（r = -0.01，P =.88）或UCHL1（r = -0.05，P =.60）无关，而白蛋白呈弱负相关：p-tau181（r = -0.18，P <.01）、NfL（r = -0.22，P <.01）、GFAP（r = -0.17，P <.05）、t-tau（r = -0.20，P =.02）和UCHL1（r = -0.15，P =.09）。
肝硬化患者p-tau181、NfL和t-tau升高与肾功能损害和低白蛋白血症有关，提示在解释神经病理学血浆生物标志物时，肝肾功可能很重要。
