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Computational Repurposing of Bumetanide for Preventing or Treating Alzheimer’s Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE182765 | GEO | 2021/10/03

REPOSITORIES: GEO

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Computational Repurposing of Bumetanide for Preventing or Treating Alzheimer’s Disease [AT01_J20_apoEKI_Bumex_snRNA-seq]

Project description:The evident genetic, pathological, and clinical heterogeneity of Alzheimer’s disease (AD) poses challenges for traditional drug development. We conducted a computational drug repurposing screen for drugs to treat apolipoprotein (apo) E4-related AD. We first established apoE-genotype-dependent transcriptomic signatures of AD by analyzing publicly-available human brain database. We then queried these signatures against the Connectivity Map database containing transcriptomic perturbations of >1300 drugs to identify those that best reverse apoE-genotype-specific AD signatures. Bumetanide was identified as a top drug for apoE4 AD. Bumetanide treatment of apoE4 mice without or with Ab accumulation rescued electrophysiological, pathological, or cognitive deficits. Single-nucleus RNA-sequencing revealed transcriptomic reversal of AD signatures in specific cell types in these mice, a finding confirmed in apoE4-iPSC-derived neurons. In humans, bumetanide exposure was associated with a significantly lower AD prevalence in individuals over the age of 65 in two EHR databases, suggesting effectiveness of bumetanide in preventing AD.

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Computational Repurposing of Bumetanide for Preventing or Treating Alzheimer’s Disease [AT01_J20_apoEKI_Bumex_snRNA-seq]

Project description:Computational Repurposing of Bumetanide for Preventing or Treating Alzheimer’s Disease [AT01_J20_apoEKI_Bumex_snRNA-seq]

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