Raghavan Sheelakumari, Graff-Radford Jonathan, Hofrenning Ekaterina, Fought Angela J, Reid Robert I, Kamykowski Michael G, Algeciras-Schimnich Alicia, Windham B Gwen, Knopman David S, Lowe Val J, Jack Clifford R, Petersen Ronald C, Vemuri Prashanthi
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Neurology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Alzheimers Dement. 2025 Jun;21(6):e70381. doi: 10.1002/alz.70381.
We investigated the usefulness of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for capturing vascular cognitive impairment (VCI) in the context of amyloidosis.
Using two independent cohorts (n = 1810), we assessed the relationship of plasma NfL and GFAP with (1) vascular brain indices; (2) diagnostic states using the following definitions: vascular versus not (white matter hyperintensity/total intracranial volume ≥ 1.3%), and cognitively impaired (CI) versus cognitively unimpaired (CU) using Clinical Dementia Rating ([CDR] scale ≥ 0.5); and (3) their upstream predictors using structural equation models (SEMs).
Plasma NfL and GFAP were associated with vascular brain damage and differed across states (VCI > vascular CU > non-vascular CI > non-vascular CU). In a population-based sample, these biomarkers distinguished vascular CU and VCI from non-vascular CU groups with greater separation in amyloid negative participants. Pathway analyses showed NfL was primarily influenced by systemic/brain vascular health, whereas amyloid contributed to GFAP variability.
Plasma biomarkers, particularly NfL, capture vascular brain changes and show promise for VCI identification.
Plasma NfL and glial fibrillary acidic protein (GFAP) were associated with vascular brain indices. Plasma biomarkers differed across diagnostic states (VCI > vascular CU > non-vascular CI > non-vascular CU). Plasma markers discriminated vascular from non-vascular states with greater separation in Aβ- participants. NfL was linked to vascular health, while amyloid influenced GFAP variability in the population-based sample. Future longitudinal frameworks should consider systemic inflammation markers along with these plasma markers to better understand VCID-related brain changes and cognitive decline.
我们研究了血浆神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）在淀粉样变性背景下用于识别血管性认知障碍（VCI）的效用。
我们使用两个独立队列（n = 1810），评估血浆NfL和GFAP与以下因素的关系：（1）脑血流灌注指标；（2）诊断状态，采用以下定义：血管性与非血管性（白质高信号/总颅内体积≥1.3%），以及认知障碍（CI）与认知未受损（CU），使用临床痴呆评定量表（[CDR]量表≥0.5）；（3）使用结构方程模型（SEM）分析它们的上游预测因素。
血浆NfL和GFAP与脑血流灌注损伤相关，且在不同状态下存在差异（VCI > 血管性CU > 非血管性CI > 非血管性CU）。在基于人群的样本中，这些生物标志物能够区分血管性CU和VCI与非血管性CU组，在淀粉样蛋白阴性参与者中区分度更大。通路分析表明，NfL主要受全身/脑血管健康影响，而淀粉样蛋白则导致GFAP的变异性。
血浆生物标志物，尤其是NfL，能够反映脑血流灌注变化，有望用于识别VCI。
血浆NfL和胶质纤维酸性蛋白（GFAP）与脑血流灌注指标相关。血浆生物标志物在不同诊断状态下存在差异（VCI > 血管性CU > 非血管性CI > 非血管性CU）。血浆标志物能够区分血管性与非血管性状态，在Aβ阴性参与者中区分度更大。在基于人群的样本中，NfL与血管健康相关，而淀粉样蛋白影响GFAP的变异性。未来的纵向研究框架应考虑全身炎症标志物以及这些血浆标志物，以更好地理解与VCI相关的脑血流灌注变化和认知衰退。
