Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.
Natalie DiProspero, Mithra Sathishkumar, John Janecek, Anna Smith, Liv McMillan, Melissa Petersen, Nicholas Tustison, David B Keator, Eric Doran, Christy L Hom, Dana Nguyen, Howard Andrews, Sharon Krinsky-McHale, Adam M Brickman, H Diana Rosas, Florence Lai, Elizabeth Head, Mark Mapstone, Wayne Silverman, Ira T Lott, Sid O'Bryant, Michael A Yassa
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引用次数: 0
Abstract
Introduction: 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.
Methods: 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.
Results: 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.
Discussion: 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.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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