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

Nat Neurosci. 2020 Jun;23(6):696-700. doi: 10.1038/s41593-020-0635-5. Epub 2020 May 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / complications
  • Alzheimer Disease / metabolism*
  • Databases, Factual
  • Humans
  • Intracranial Arteriosclerosis / complications
  • Intracranial Arteriosclerosis / metabolism*
  • Nerve Tissue Proteins / biosynthesis*
  • Prefrontal Cortex / metabolism*
  • Proteomics*


  • Nerve Tissue Proteins