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Ciencia básica y patogénesis
Tengfei Li1, Xifeng Wang1, Martin Cole2
1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
Resumen
El amiloide-beta (Aβ) impacta el deterioro cognitivo en la enfermedad de Alzheimer (EA) en parte a través de cambios en la conectividad estructural del cerebro, específicamente la anisotropía fraccional (FA) en las redes visual, del modo por defecto (DMN) y frontoparietal (FPN).
Área de la Ciencia:
- Neuroimaging
- Neuroscience
- Alzheimer's Disease Research
Sus antecedentes:
- Alzheimer's Disease (AD) is characterized by cognitive decline.
- Amyloid-beta (Aβ) accumulation is a key pathological hallmark of AD.
- Brain structural connectivity alterations may mediate Aβ's effects on cognition.
Objetivo del estudio:
- To investigate how brain structural connectivity mediates the impact of Aβ on cognitive decline in AD.
- To identify specific brain networks and pathways involved in this mediation process.
Principales métodos:
- Utilized fibertracking tractography and fiber clustering on the ADNI2 dataset.
- Computed mean fractional anisotropy (FA) and analyzed associations with CSF Aβ42 and cognitive scores (MMSE).
- Employed linear mixed models and FDR-adjusted mediation analyses, controlling for confounders.
Principales resultados:
- 16 fibers showed mediation of Aβ's effect on MMSE, primarily within visual, DMN, and FPN networks.
- Aβ positively associated with FA in DMN or FPN-related fibers during early AD phases.
- FA changes mediated 21.6% of Aβ's impact on cognitive decline.
Conclusiones:
- Brain structural connectivity, particularly FA within visual, DMN, and FPN networks, partially mediates Aβ's effect on cognitive decline in AD.
- DMN and FPN connectivity are notably susceptible in the early stages of AD.
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