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Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity

GSE235076 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/06/30 Platform GPL23479
Summary
Apolipoprotein E (apoE) plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). In the brain, apoE is predominantly expressed and secreted by astrocytes, but is dramatically up-regulated in microglia under AD-associated conditions. Although the function of astrocytic apoE has been widely investigated, whether and how apoE particles derived from different types of glia differ in biological features and function remains elusive. Here, we show that apoE particles derived from astrocytes and microglia exhibit dissimilar sizes. Microglial apoE particles impaired neurite growth and synapses and promoted neuronal senescence, whereas GPNMB-deficient microglial apoE particles abolished these detrimental effects. These findings provide direct evidence supporting that microglia-derived apoE particles contribute to neuronal senescence and toxicity.
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Also filed as BioProject PRJNA984297 and SRA study SRP444275. Searching any of these in the dataset finder brings you back here.

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