Age-associated cortical similarity networks correlate with cell type-specific transcriptional signatures

Abstract Human brain structure shows heterogeneous patterns of change across adults aging and is associated with cognition. However, the relationship between cortical structural changes during aging and gene transcription signatures remains unclear. Here, using structural magnetic resonance imaging data of two separate cohorts of healthy participants from the Cambridge Centre for Aging and Neuroscience (n = 454, 18–87 years) and Dallas Lifespan Brain Study (n = 304, 20–89 years) and a transcriptome dataset, we investigated the link between cortical morphometric similarity network and brain-wide gene transcription. In two cohorts, we found reproducible morphometric similarity network change patterns of decreased morphological similarity with age in cognitive related areas (mainly located in superior frontal and temporal cortices), and increased morphological similarity in sensorimotor related areas (postcentral and lateral occipital cortices). Changes in morphometric similarity network showed significant spatial correlation with the expression of age-related genes that enriched to synaptic-related biological processes, synaptic abnormalities likely accounting for cognitive decline. Transcription changes in astrocytes, microglia, and neuronal cells interpreted most of the age-related morphometric similarity network changes, which suggest potential intervention and therapeutic targets for cognitive decline. Taken together, by linking gene transcription signatures to cortical morphometric similarity network, our findings might provide molecular and cellular substrates for cortical structural changes related to cognitive decline across adults aging.