DiProspero Natalie, Sathishkumar Mithra, Janecek John, Smith Anna, McMillan Liv, Petersen Melissa, Tustison Nicholas, Keator David B, Doran Eric, Hom Christy L, Nguyen Dana, Andrews Howard, Krinsky-McHale Sharon, Brickman Adam M, Rosas H Diana, Lai Florence, Head Elizabeth, Mapstone Mark, Silverman Wayne, Lott Ira T, O'Bryant Sid, Yassa Michael A
Department of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USA.
Center for the Neurobiology of Learning and Memory University of California Irvine California USA.
Alzheimers Dement (Amst). 2024 Feb 12;16(1):e12542. doi: 10.1002/dad2.12542. eCollection 2024 Jan-Mar.
Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS.
T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory.
Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory.
The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.
几乎所有唐氏综合征（DS）患者都会出现与阿尔茨海默病（AD）相关的神经病理学改变。海马体和内嗅皮质（EC）萎缩，以及血浆神经丝轻链（NfL）蛋白浓度升高，是与晚发性AD相关的神经退行性变的标志物。我们假设，海马体和EC灰质减少以及血浆NfL浓度升高与DS成年患者的记忆力有关。
收集了101名DS参与者的T1加权结构磁共振成像（MRI）数据。得出了海马体和EC体积以及EC亚区域皮质厚度。在一部分参与者中，获得了血浆NfL浓度和改良线索回忆测试分数。使用偏相关和中介分析来检验内侧颞叶（MTL）萎缩、血浆NfL和情景记忆之间的关系。
海马体体积、左侧前外侧EC（alEC）厚度和血浆NfL相互关联，且与记忆力有关。血浆NfL介导了左侧alEC厚度与记忆力以及海马体体积与记忆力之间的关系。
MTL灰质与记忆力之间的关系由血浆NfL水平介导，这表明在DS患者中，轴突损伤背后的神经退行性变过程与支持情景记忆的关键结构中明显的灰质损失之间存在联系。
