There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia.

We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.

Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.

Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.

在衰老和神经退行性疾病研究中，直接比较血浆神经丝光 (NfL) 和胶质纤维酸性蛋白 (GFAP) 的数据很少。我们在诊断为临床正常 (CN)、轻度认知障碍 (MCI) 或阿尔茨海默氏痴呆的两个独立老年人队列中评估了血浆 NfL 和血浆 GFAP 与脑容量和认知的关联。

我们研究了 121 名参与者（队列 1：n = 50，年龄 71.6 ± 6.9 岁，78% CN，22% MCI；队列 2：n = 71，年龄 72.2 ± 9.2 岁，45% CN，25% MCI，30%痴呆）。获得全脑和广泛的感兴趣子区域 (ROI) 的灰质和白质体积。神经心理学测试评估了记忆、执行功能、语言和视觉空间能力。使用单分子阵列测定 (Quanterix Simoa) 一式两份地分析血浆样品的 NfL 和 GFAP。具有结构 MRI 和认知结果的线性回归模型同时包括血浆 NfL 和 GFAP 以及相关协变量。

在颞叶（队列 1：β = -0.33，p = .002；队列 2：β = -0.36，p = .03）和顶叶 ROI（队列 1：β = −0.31，p = .01；队列 2：β = −0.35，p = .04）。对于灰质体积，没有出现一致的发现。较高的血浆 GFAP 与较低的执行功能评分相关（队列 1：β = −0.38，p = .01；队列 2：β = −0.36，p=.007）。血浆 NfL 与灰质或白质体积或调整血浆 GFAP 后的认知无关。

血浆 GFAP 可能比血浆 NfL 对白质和认知变化更敏感。反映星形胶质细胞病理生理学的生物标志物可能捕捉到衰老和神经退行性疾病的复杂动态。