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April 29, 2026Degenerative Neurological and Neuromuscular DiseaseOpen Access

The Gut-Brain Axis in Alzheimer’s: From Microbiota Genetics to Stigmasterol’s Neuroprotection Mechanism

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Authors

TDTunan DingJCJunlei Chen向向云胜

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Overview

Randomized trial identifies stigmasterol's neuroprotective effects in Alzheimer’s, suggesting new treatment strategies.

Key Points

  • This study aims to explore the gut-brain axis's role in Alzheimer's disease and discover natural compounds for therapy.
  • Utilized Mendelian randomization to infer the relationship between gut microbiota and Alzheimer's disease.
  • Combined Summary-data-based Mendelian randomization with single-cell and spatial transcriptomics.
  • Validated stigmasterol's effects in vitro on Aβ 1-42 exposed SH-SY5Y cells.
  • Desulfovibrio identified as a risk factor for Alzheimer's; Slackia and Lachnospiraceae NK4A136 shown as protective.
  • Confirmed STIM1-mediated calcium signaling as a crucial pathway affecting neuroprotection.
  • Stigmasterol significantly reduced Aβ 1-42 induced neuronal apoptosis, modulating the STIM1/Orai1 pathway and Bcl-2/Bax ratio.

Cite This Study

Ding et al. (2026) studied this question.

synapsesocial.com/papers/69f19f16edf4b4682480629ahttps://doi.org/10.2147/dnnd.s580890
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