Neurofilament Light Chain Concentration Mediates the Association Between Regional Medial Temporal Lobe Structure and Memory in Adults with Down Syndrome

Overview

Journal Alzheimers Dement (Amst)

Date 2024 Feb 13

PMID 38348178

Authors

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 OBryant

Michael A Yassa

Affiliations

Soon will be listed here.

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.

Citing Articles

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

DiProspero N, Sathishkumar M, Janecek J, Smith A, McMillan L, Petersen M Alzheimers Dement (Amst). 2024; 16(1):e12542.

PMID: 38348178 PMC: 10859879. DOI: 10.1002/dad2.12542.

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