Global Deficiency of Alzheimer's Disease Risk Gene <i>Il1rap</i> Reduces Pathological Tau in a Mouse Model of Systemic Inflammation.

ABSTRACT: Brain inflammation is strongly associated with neurodegeneration in Alzheimer's disease (AD) and related tauopathies. We have previously demonstrated that microglia-derived interleukin-1β (IL-1β) induces tau hyperphosphorylation in a cell-autonomous manner and depends on activating the IL-1 receptor (IL-1R1) signaling pathway. IL-1 receptor accessory protein (IL-1RAcP) is a co-receptor for IL-1R1 and is essential for the IL-1R1 receptor function and downstream signaling. Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) in the IL1RAP gene that have been shown to increase AD risk. Here, we demonstrate that global and neuron-specific isoform deficiency of IL-1RAcP regulates hyperphosphorylated tau levels in a lipopolysaccharide (LPS)-induce

SUBMITTER: Dadras S 

PROVIDER: S-EPMC12688222 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature