Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain

Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and between RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer's disease, suggesting shared mechanisms. Proteome-wide association studies of brain samples from older adults revealed effects of cerebral atherosclerosis and Alzheimer's disease. A subset of proteins and protein co-expression modules were associated with both, suggesting shared mechanisms.