Biomolecules · Oct 26, 2026
Single-Cell and Spatial Transcriptomic Perspectives on Brain Ageing and Alzheimer Disease Neuroinflammation: Shared Programs and Disease-Related Reorganization
By Guan J, Li X, Huang L
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.