Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation.

ABSTRACT:

Introduction

Proteostasis dysfunction is a hallmark of frontotemporal dementia (FTD) and Alzheimer's disease (AD), yet the genetic and molecular pathways that disrupt protein homeostasis remain poorly understood.

Methods

We integrated human genetics, transcriptomics, and functional studies to identify proteostasis network components involved in tauopathy.

Results

We identified 18 proteostasis network genes harboring 75 rare, damaging variants enriched in FTD and/or AD. These genes, spanning multiple proteostasis pathways, were differentially expressed in MAPT mutant neurons and dysregulated in FTD and AD brains. NINL, which encodes Nlp, emerged as the only gene consistently upregulated across all datasets. NINL overexpression reduced tau seeding a

SUBMITTER: Swift SK 

PROVIDER: S-EPMC12724438 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature