Single-Cell and Spatial Transcriptomic Perspectives on Brain Ageing and Alzheimer Disease Neuroinflammation: Shared Programs and Disease-Related Reorganization
- 1School of Life Science and Technology, Xidian University, Xi’an 710126, China
Abstract
Ageing is a major biological context for late-onset Alzheimer disease (AD), but its relationship with AD neuroinflammation remains incompletely understood. This review compares immune and glial changes in physiological brain ageing and AD using single-cell, single-nucleus, and spatial transcriptomic studies of human tissue and experimental models. Interferon response, phagocytic, and lipid-handling gene programs recur in both settings, while their cellular sources and spatial distributions vary with brain region, genotype, and pathology. Myelin-associated responses in aged white matter and plaque-associated glial environments in AD show how similar programs occur around different substrates. Tau-associated and vascular changes provide further tissue contexts for comparison. Most human studies are cross-sectional, so molecular similarity or spatial co-occurrence cannot establish functional equivalence or a causal progression from ageing to AD. Combining expression profiles with genetic perturbation, cellular function, and tissue localization can guide mechanistic testing and biomarker development.
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BibTeX
@article{guan2026singlecell,
title = {{Single-Cell and Spatial Transcriptomic Perspectives on Brain Ageing and Alzheimer Disease Neuroinflammation: Shared Programs and Disease-Related Reorganization}},
author = {Jingjing Guan and Xiao Li and Liyu Huang},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111562},
url = {https://www.mdpi.com/2218-273X/16/11/1562},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-Cell and Spatial Transcriptomic Perspectives on Brain Ageing and Alzheimer Disease Neuroinflammation: Shared Programs and Disease-Related Reorganization
AU - Jingjing Guan
AU - Xiao Li
AU - Liyu Huang
PY - 2026
DA - 2026/10/26
JO - Biomolecules
DO - 10.3390/biom16111562
UR - https://www.mdpi.com/2218-273X/16/11/1562
AB - Ageing is a major biological context for late-onset Alzheimer disease (AD), but its relationship with AD neuroinflammation remains incompletely understood. This review compares immune and glial changes in physiological brain ageing and AD using single-cell, single-nucleus, and spatial transcriptomic studies of human tissue and experimental models. Interferon response, phagocytic, and lipid-handling gene programs recur in both settings, while their cellular sources and spatial distributions vary with brain region, genotype, and pathology. Myelin-associated responses in aged white matter and plaque-associated glial environments in AD show how similar programs occur around different substrates. Tau-associated and vascular changes provide further tissue contexts for comparison. Most human studies are cross-sectional, so molecular similarity or spatial co-occurrence cannot establish functional equivalence or a causal progression from ageing to AD. Combining expression profiles with genetic perturbation, cellular function, and tissue localization can guide mechanistic testing and biomarker development.
SN - 2218-273X
ER -