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Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors

GSE300690 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/15 Platform GPL24247
Summary
Overexpression of the low-density lipoprotein receptor (LDLR) is known to decrease apolipoprotein E (APOE) levels and alleviate amyloid beta (Aβ) pathology. We hypothesized that inhibiting the Inducible Degrader of LDLR (IDOL), an enzyme that ubiquitinates LDLR for degradation, would increase endogenous LDLR levels and attenuate amyloid pathology. To investigate the cell-type–specific role of IDOL, we generated Idol conditional knockout mice on an Aβ-amyloidosis mouse model and performed biochemical, histological, and multi-omics analyses. We demonstrated that neuronal, but not microglial, Idol deletion reduced amyloid accumulation and altered brain LDLR and APOE levels, indicating the critical role of neuronal IDOL-LDLR in amyloid pathology. In addition, neuronal Idol deletion increased the levels of Reelin receptors important for synaptic function, and single-nuclei RNA sequencing revealed significant changes associated with synaptic organization.
Published in
Deletion of neuronal Idol ameliorates Alzheimer's disease-related pathologies via APOE receptors
Karahan H, Hartigan K, Al-Amin MM et al. · Alzheimer's & dementia : the journal of the Alzheimer's Association 2025 · PMID 41384508 · doi:10.1002/alz.70949
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Also filed as BioProject PRJNA1281672 and SRA study SRP594357. Searching any of these in the dataset finder brings you back here.

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