Transcriptomic and protein analysis of human cortex reveals genes and pathways linked to NPTX2 disruption in Alzheimer's disease.

ABSTRACT: The expression of NPTX2, a neuronal immediate early gene (IEG) essential for excitatory-inhibitory balance, is altered in the earliest stages of cognitive decline that anticipate Alzheimer's disease (AD). Here, we use NPTX2 as a point of reference for Omics studies to identify genes and pathways linked to its position in AD onset and progression. We integrated bulk RNA sequencing from 575 middle temporal gyrus (MTG) samples across four cohorts together with targeted proteomics in the same samples using parallel reaction monitoring-mass spectrometry in 135 representative cases, focusing on 20 curated proteins spanning synaptic, trafficking, lysosomal, and regulatory categories. NPTX2 RNA and protein were significantly reduced in AD, and to a lesser extent in mild cognitive impairment (MCI)

SUBMITTER: Lao Y 

PROVIDER: S-EPMC12633229 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature