U1-70K and U1A and tau pathogenesis in demented and non-demented individuals with Down syndrome.

ABSTRACT:

Introduction

Splicing protein mislocalization is associated with tau pathogenesis, but its role in Down syndrome (DS) is under-investigated.

Methods

Spliceosome associations with tau and plaque pathology were examined in frontal cortex from DS with dementia (DSD+) and without dementia (DSD-) using quantitative immunoblotting and immunohistochemistry.

Results

U1-70K and U1A levels were downregulated, and hnRNPA2B1, 3Rtau, and 4Rtau were upregulated, whereas SRSF2 and CLK1 were unchanged in DSD+. The number of U1-70K lightly labeled cells was only greater in layer III in DSD+. U1A intensely stained nuclei decreased significantly in layer III in DSD+, whereas those lightly labeled significantly increased in layers III and V-VI in DSD+. U1 mislocalization and tangles appe

SUBMITTER: Perez SE 

PROVIDER: S-EPMC12322699 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature