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Disruption of cortical cell type composition and function underlies diabetes‑associated cognitive decline – published online 23/06/2023

Little graphical abstract

Karis Little, Aditi Singh, Angel Del Marco, María Llorian‑Salvador, Maria Vargas‑Soria, Mireia Turch‑Anguera, Montse Solé, Noëlle Bakker, Sarah Scullion, Joan X. Comella, Ingeborg Klaassen, Rafael Simó, Monica Garcia‑Alloza, Vijay K. Tiwari, Alan W. Stitt, on behalf of the RECOGNISED consortium

People with type-2 diabetes are at higher risk of cognitive decline and dementia; however, the cellular changes that occur in the brain as type 2 diabetes progresses remain poorly understood. In this issue, Little, Singh and Del Marco et al ( describe using single-cell RNA sequencing to investigate changes to the neurovascular unit (NVU) within the cerebral cortex in a mouse model of type 2 diabetes. The authors identified distinct transcriptional signatures in a number of key neuronal, glial vascular and immune cells, demonstrating that metabolic and inflammatory processes are dysregulated in the cortical glia of diabetic mice. In parallel, they report that neuronal maturation was significantly affected in the type 2 diabetes cortex, with these changes occurring alongside evident cognitive decline and vascular damage. They further demonstrate that post-mortem cortex from individuals with type 2 diabetes showed comparable changes to what was observed in the mouse model. The authors conclude that altered metabolic function, neuroinflammation and changes to neuronal maturation may play an integral role in NVU damage and thus cognitive decline in type 2 diabetes.

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