Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome
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 neurode...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/dad2.12542 |
| _version_ | 1827307493995315200 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Natalie DiProspero |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T18:41:02Z |
| format | Article |
| id | doaj.art-7422d877af6a4072bb0972d4b84616f7 |
| institution | Directory Open Access Journal |
| issn | 2352-8729 |
| language | English |
| last_indexed | 2024-04-24T18:41:02Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| spelling | doaj.art-7422d877af6a4072bb0972d4b84616f72024-03-27T13:14:40ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-01-01161n/an/a10.1002/dad2.12542Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndromeNatalie DiProspero0Mithra Sathishkumar1John Janecek2Anna Smith3Liv McMillan4Melissa Petersen5Nicholas Tustison6David B. Keator7Eric Doran8Christy L. Hom9Dana Nguyen10Howard Andrews11Sharon Krinsky‐McHale12Adam M. Brickman13H. Diana Rosas14Florence Lai15Elizabeth Head16Mark Mapstone17Wayne Silverman18Ira T. Lott19Sid O'Bryant20Michael A. Yassa21Department of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USAInstitute for Translational Research University of North Texas Health Science Center Fort Worth Texas USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USADepartment of Psychiatry and Behavioral Sciences School of Medicine University of California Irvine California USADepartment of Pediatrics School of Medicine University of California Irvine California USADepartment of Pediatrics School of Medicine University of California Irvine California USADepartment of Pediatrics School of Medicine University of California Irvine California USADepartment of Psychiatry College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology Massachusetts General Hospital Boston Massachusetts USADepartment of Neurology Massachusetts General Hospital Boston Massachusetts USACenter for the Neurobiology of Learning and Memory University of California Irvine California USACenter for the Neurobiology of Learning and Memory University of California Irvine California USADepartment of Pediatrics School of Medicine University of California Irvine California USADepartment of Pediatrics School of Medicine University of California Irvine California USAInstitute for Translational Research University of North Texas Health Science Center Fort Worth Texas USADepartment of Neurobiology and Behavior School of Biological Sciences University of California Irvine California USAAbstract 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.https://doi.org/10.1002/dad2.12542Alzheimer's diseaseanterolateral entorhinal cortexcognitive declinedementiaDown syndromeepisodic memory |
| spellingShingle | 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 Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring Alzheimer's disease anterolateral entorhinal cortex cognitive decline dementia Down syndrome episodic memory |
| title | Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome |
| title_full | Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome |
| title_fullStr | Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome |
| title_full_unstemmed | Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome |
| title_short | Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome |
| title_sort | neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with down syndrome |
| topic | Alzheimer's disease anterolateral entorhinal cortex cognitive decline dementia Down syndrome episodic memory |
| url | https://doi.org/10.1002/dad2.12542 |
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