Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
J Alzheimers Dis. 2023;92(3):887-898. doi: 10.3233/JAD-221015.
The National Institute on Aging-Alzheimer's Association Research Framework proposes defining Alzheimer's disease by grouping imaging and fluid biomarkers by their respective pathologic processes. The AT(N) structure proposes several neurodegenerative fluid biomarkers (N) including total tau (t-tau), neurogranin (Ng), and neurofilament light chain (NfL). However, pathologic drivers influencing each biomarker remain unclear.
To determine whether cerebrospinal fluid (CSF)-neurodegenerative biomarkers (N) map differentially to Alzheimer's disease pathology measured by Aβ42 (an indicator of amyloidosis, [A]), p-tau (an indicator of tau deposition, [T]), and MRI vascular pathology indicators (measured by white-matter integrity, infarcts, and microbleeds [V]).
Participants were from Mayo Clinic Study of Aging (MCSA) with CSF measures of NfL, Ng, t-tau, Aβ42, and p-tau and available MRI brain imaging. Linear models assessed associations between CSF neurodegeneration (N) markers, amyloid markers (A), tau (T), and vascular pathology (V).
Participants (n = 408) had a mean age of 69.2±10.7; male, 217 (53.2%); cognitively unimpaired, 359 (88%). All three neurodegeneration biomarkers correlated with age (p < 0.001 for NfL and t-tau, p = 0.018 for Ng). Men had higher CSF-NfL levels; women had higher Ng (p < 0.001). NfL and t-tau levels correlated with infarcts (p = 0.009, p = 0.034 respectively); no biomarkers correlated with white-matter integrity. N biomarkers correlated with p-tau levels (T, p < 0.001). Higher Aβ42 levels associated with higher N-biomarker levels but only among cognitively unimpaired (A, p < 0.001).
The influence of vascular pathology in the general population on CSF (N) biomarkers is modest, with greater influence of infarcts than white-matter disruption. Neurodegeneration markers more closely correlated with tau than amyloid markers.
美国国家老龄化研究所-阿尔茨海默病协会研究框架提出通过其各自的病理过程将影像学和液体生物标志物进行分组，以定义阿尔茨海默病。AT（N）结构提出了几种神经退行性液体生物标志物（N），包括总 tau（t-tau）、神经颗粒蛋白（Ng）和神经丝轻链（NfL）。然而，影响每种生物标志物的病理驱动因素仍不清楚。
确定脑脊液（CSF）-神经退行性生物标志物（N）是否可以不同程度地映射到通过 Aβ42（淀粉样蛋白的指标，[A]）、p-tau（tau 沉积的指标，[T]）和 MRI 血管病理指标（通过白质完整性、梗死和微出血[V]来测量）测量的阿尔茨海默病病理。
参与者来自梅奥诊所衰老研究（MCSA），具有 CSF 中 NfL、Ng、t-tau、Aβ42 和 p-tau 的测量值以及可用的 MRI 脑成像。线性模型评估了 CSF 神经退行性变（N）标志物、淀粉样蛋白标志物（A）、tau（T）和血管病理标志物（V）之间的相关性。
参与者（n=408）的平均年龄为 69.2±10.7；男性，217（53.2%）；认知正常，359（88%）。所有三种神经退行性生物标志物均与年龄相关（NfL 和 t-tau 为 p<0.001，Ng 为 p=0.018）。男性 CSF-NfL 水平较高；女性 Ng 水平较高（p<0.001）。NfL 和 t-tau 水平与梗死相关（p=0.009，p=0.034）；没有生物标志物与白质完整性相关。N 生物标志物与 p-tau 水平相关（T，p<0.001）。较高的 Aβ42 水平与较高的 N 生物标志物水平相关，但仅在认知正常的人群中相关（A，p<0.001）。
在普通人群中，血管病理对 CSF（N）生物标志物的影响较小，梗死的影响大于白质破坏。神经退行性变标志物与 tau 标志物的相关性大于与淀粉样蛋白标志物的相关性。
