2026-02-12 カリフォルニア大学アーバイン校(UCI)
<関連情報>
- https://news.uci.edu/2026/02/12/uc-irvine-led-team-creates-first-cell-type-specific-gene-regulatory-maps-for-alzheimers-disease/
- https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71053
相関関係から因果関係へ:アルツハイマー病における細胞型特異的遺伝子制御ネットワーク From correlation to causation: cell-type-specific gene regulatory networks in Alzheimer’s disease
Danni Liu, Zhongli Jiang, Hyunjin Kim, Anke M. Tukker, Ashish Dalvi, Junkai Xie, Yan Li, Chongli Yuan, Aaron B. Bowman, Dabao Zhang, Min Zhang
Alzheimer’s & Dementia Ppublished: 12 February 2026
DOI:https://doi.org/10.1002/alz.71053
Abstract
INTRODUCTION
Alzheimer’s disease (AD) involves complex regulatory disruptions across multiple brain cell types, yet the comprehensive intracellular causal mechanisms remain poorly understood.
METHODS
We present an integrative analysis framework using single-nucleus transcriptomics with matched subject-level genotype data from 272 AD patients in the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and construct causality-based, cell-type-specific gene regulatory networks (GRNs).
RESULTS
Our method identifies regulatory genes among transcription factors (TFs) and non-TFs, generating a complete and accurate causal regulatory map across brain cell types. Our analyses reveal both established and novel regulations, pathways, and cell-type-specific hub genes in AD. Beyond constructing transcriptome-wide GRNs, we quantitatively evaluate hub genes and distinguish those with regulatory versus responsive roles.
DISCUSSION
Our study provides a comprehensive map of cell-type-specific causal GRNs in AD, with a methodology applicable to other complex diseases such as cancer, enabling dynamic pathway exploration, hypothesis generation, and functional interpretation.
Highlights
- Comprehensive causal regulatory maps across six brain cell types revealed cell-type-specific regulatory mechanisms that move beyond traditional correlation-based and TF-centric model limitations.
- Novel and established hub genes and functional modules were compared across cell types, providing insights into cellular functions related to AD.
- Hub gene roles as regulators or targets were quantitatively evaluated within cell-type GRNs.
- The constructed GRNs show upstream non-TF genes regulating TFs and interconnected TF regulatory modules, highlighting the complexity of AD regulatory mechanisms beyond TF-centric assumptions.
