Lee Ann J, Howard Erica, Saltiel Nicole, Hayes Jasmeet P, Hayes Scott M
Department of Psychology, The Ohio State University, Columbus, OH 43210, USA.
Chronic Brain Injury Initiative, The Ohio State University, Columbus, OH 43210, USA.
Brain Commun. 2025 Feb 14;7(1):fcaf068. doi: 10.1093/braincomms/fcaf068. eCollection 2025.
This cross-sectional study examined associations between multiple fluid biomarkers of neuronal and glial dysfunction (plasma neurofilament light chain, CSF growth-associated protein 43 and CSF soluble triggering receptor expressed on myeloid cells 2), total white matter hyperintensity volume and episodic memory and executive function performance in the context of Alzheimer's disease biomarker status. A total of 563 participants (mean age = 71.9 years, standard deviation = 7.2) from the Alzheimer's Disease Neuroimaging Initiative were classified by the amyloid-β/tau/neurodegeneration framework into no Alzheimer's disease pathology ( = 176), suspected non-Alzheimer's disease pathophysiology ( = 87) or Alzheimer's disease continuum ( = 300) groups. Participants completed baseline neuropsychological assessment, plasma/CSF biomarker collection and MRI. Analyses explored the relative contributions of biomarkers to episodic memory and executive function performance and whether relationships varied by amyloid-β/tau/neurodegeneration group status. Across all participants, neurofilament light chain ( -0.14, < 0.001) and growth-associated protein 43 ( -0.13, < 0.001) were the strongest biomarkers associated with episodic memory performance, such that greater levels were associated with worse episodic memory. There was a group by growth-associated protein 43 interaction with episodic memory: greater growth-associated protein 43 was associated with lower episodic memory performance in participants classified as Alzheimer's disease continuum relative to the no Alzheimer's disease pathology group ( -0.26, < 0.001). No robust associations between biomarkers and executive function performance or between soluble triggering receptor expressed on myeloid cells 2, white matter hyperintensity volume and cognition were observed. Biomarkers of neuro-axonal injury and synaptic dysfunction may independently contribute to episodic memory performance across participants with differing amyloid-β/tau/neurodegeneration profiles. Growth-associated protein 43 may predict worse episodic memory performance in participants with greater Alzheimer's disease pathology. These biomarkers of neuronal dysfunction may serve as domain-specific cognitive correlates in the context of Alzheimer's disease biomarker status.
这项横断面研究在阿尔茨海默病生物标志物状态的背景下，考察了神经元和神经胶质功能障碍的多种体液生物标志物（血浆神经丝轻链、脑脊液生长相关蛋白43和脑脊液髓样细胞表达的可溶性触发受体2）、总白质高信号体积与情景记忆及执行功能表现之间的关联。来自阿尔茨海默病神经影像倡议组织的563名参与者（平均年龄 = 71.9岁，标准差 = 7.2）根据淀粉样β蛋白/ tau蛋白/神经退行性变框架被分为无阿尔茨海默病病理组（ = 176）、疑似非阿尔茨海默病病理生理组（ = 87）或阿尔茨海默病连续体组（ = 300）。参与者完成了基线神经心理学评估、血浆/脑脊液生物标志物采集和磁共振成像。分析探讨了生物标志物对情景记忆和执行功能表现的相对贡献，以及这些关系是否因淀粉样β蛋白/ tau蛋白/神经退行性变组状态而异。在所有参与者中，神经丝轻链（ = -0.14， < 0.001）和生长相关蛋白43（ = -0.13， < 0.001）是与情景记忆表现关联最强的生物标志物，即水平越高，情景记忆越差。生长相关蛋白43与情景记忆存在组间交互作用：与无阿尔茨海默病病理组相比，在被归类为阿尔茨海默病连续体的参与者中，生长相关蛋白43水平越高，情景记忆表现越低（ = -0.26， < 0.001）。未观察到生物标志物与执行功能表现之间或髓样细胞表达的可溶性触发受体2、白质高信号体积与认知之间存在显著关联。神经轴突损伤和突触功能障碍的生物标志物可能在具有不同淀粉样β蛋白/ tau蛋白/神经退行性变特征的参与者中独立影响情景记忆表现。生长相关蛋白43可能预示着阿尔茨海默病病理程度较高的参与者情景记忆表现较差。在阿尔茨海默病生物标志物状态的背景下，这些神经元功能障碍的生物标志物可能作为特定领域的认知相关指标。
