Tsotras Melina, Charbonneau Joey A, Lepage Claude, Bennett Jeffrey L, Veraart Jelle, Evans Alan C, Bliss-Moreau Eliza, Raven Erika P
bioRxiv. 2025 Jul 12:2025.07.08.663725. doi: 10.1101/2025.07.08.663725.
Large-scale brain networks are vulnerable to change with aging and become dysregulated. How these networks are altered at the cellular level remains unclear owing to challenges of bridging data across scales. Here, we integrate cortical similarity networks with whole brain spatial transcriptomics to characterize the aging brain in a lifespan cohort of macaques (N=64, ages 1-26 years). Deep-layer excitatory neurons and oligodendrocytes emerged as dominant correlates of cortical similarity, linking infragranular cell type composition to macroscopic network structure. Age-related declines in network strength were most pronounced in transmodal networks, including default mode and limbic, and aligned with regions enriched in inhibitory and glial cell types. Parvalbumin-enriched chandelier cells showed the strongest association with regional vulnerability, suggesting a role in network disconnection. Cell-type enrichment was conserved across species, with both human and macaque transcriptomic data aligning with the cortical functional hierarchy. These findings uncover a cellular basis for cortical network aging and highlight the value of imaging-transcriptomic integration across scales.
大规模脑网络易随衰老而发生变化并出现失调。由于跨尺度数据衔接的挑战，这些网络在细胞水平上如何改变仍不清楚。在此，我们将皮质相似性网络与全脑空间转录组学相结合，以在一个猕猴寿命队列（N = 64，年龄1 - 26岁）中描绘衰老大脑的特征。深层兴奋性神经元和少突胶质细胞成为皮质相似性的主要相关因素，将颗粒下层细胞类型组成与宏观网络结构联系起来。网络强度与年龄相关的下降在跨模态网络中最为明显，包括默认模式和边缘系统，并与富含抑制性和胶质细胞类型的区域一致。富含小白蛋白的吊灯细胞与区域易损性表现出最强的关联，表明其在网络断开连接中起作用。细胞类型富集在物种间是保守的，人类和猕猴的转录组数据均与皮质功能层次结构相符。这些发现揭示了皮质网络衰老的细胞基础，并突出了跨尺度成像 - 转录组整合的价值。
