Evidence map›Paper›PMID 40476223›Full record

ArticleIBRO neuroscience reports2025

Potential Mediating Role of Polygenic Hazard Score in the Association Between Neurofilament Light Chain and Default Mode Network Connectivity Across the Alzheimer's Disease Continuum.

Parsa Saberian, Hamide Nasiri, Fatemeh Kaffashian, Parisa Nasiriansari, Fatemeh Nazari Nasab, Niusha Mehrvarz, Fatemeh Talebizadeh, Shayan Shakeri, Mahsa Mayeli, Alzheimer’s Disease Neuroimaging Initiative

Abstract read
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Article in IBRO neuroscience reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Parsa SaberianStudent Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Hamide NasiriStudent Research Committee,School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Fatemeh KaffashianMazandaran University of Medical Sciences, Mazandaran, Iran.
Parisa NasiriansariBiology Department, University of Mazandaran, Mazandaran, Iran.
Fatemeh Nazari NasabLorestan University of Medical Sciences, Lorestan, Iran.
Niusha MehrvarzIslamic Azad University Medical Branch of Tehran, Tehran, Iran.
Fatemeh TalebizadehDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Shayan ShakeriDepartment of medical genetics, school of medicine, Shiraz university of medical sciences, Shiraz, Iran.
Mahsa MayeliSchool of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Alzheimer’s Disease Neuroimaging Initiative

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by progressive cognitive decline and disrupted brain network connectivity, particularly within the default mode network (DMN). Neurofilament light chain (NfL) serves as a biomarker for axonal injury, but the role of genetic predisposition, assessed via the Polygenic Hazard Score (PHS), in mediating the association between plasma NfL and DMN connectivity remains unclear. This study investigates whether PHS mediates the association between plasma NfL levels and DMN connectivity in individuals across different cognitive stages, including cognitively normal (CN), mild cognitive impairment (MCI), and AD. Methods: Data were extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Plasma NfL concentrations were measured using the Simoa assay, and resting-state fMRI (rs-fMRI), assessed DMN connectivity. The cohort included 102 participants (nCN=28, nMCI=52, and nAD=22). Partial correlation analyses and mediation models were performed, adjusting for age and gender. Statistical significance was set at p < 0.05, after corrections for multiple comparisons. Results: Plasma NfL levels were significantly higher in AD group compared to CN and MCI groups (p = 0.030). DMN connectivity showed substantial declines in the AD group, particularly in the posterior and ventral regions. Significant negative correlations were observed between plasma NfL and ventral DMN connectivity in AD. However, mediation analysis indicated no significant indirect effect of PHS, suggesting that genetic risk does not mediate the plasma NfL-DMN association. Conclusion: These findings suggest that elevated plasma NfL levels are associated with disrupted ventral DMN connectivity in AD, reflecting neurodegeneration-related network dysfunction. However, the lack of a mediating effect by PHS indicates that this relationship is likely independent of genetic risk burden. Clinical Trial Number: not applicable.

Indexed as

Alzheimer's diseaseNeurofilament lightPolygenic Hazard ScoreResting-state fMRI

Identifiers

PMID40476223
PMCPMC12139489

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.