Cerebrovascular Senescence Is Associated With Tau Pathology in Alzheimer’s Disease
Bryant AG, Hu M, Carlyle BC, Arnold SE, Frosch MP, Das S, Hyman BT, Bennett RE. Cerebrovascular Senescence Is Associated With Tau Pathology in Alzheimer’s Disease. Front Neurol. 2020 Sep 16;11:575953. doi: 10.3389/fneur.2020.575953. PMID: 33041998; PMCID: PMC7525127.
This paper examines the relationship between cerebrovascular senescence and AD-related tau pathology. Vascular dysfunction is increasingly implicated in AD pathogenesis. There is evidence to suggest that tau pathology may interact with endothelial cell changes to drive vascular impairment in AD. Cellular senescence and tau NFT formation have shown a positive feedback relationship and suppression of senescence prevents tau aggregation. They examined whether endothelial senescence contributes to microvascular alterations in tau-related neurodegenerative disease using microvessels from the dorsolateral prefrontal cortex.
Results
They found upregulation of the senescence and leukocyte adhesion associated genes that are also involved in DNA damage response signalling pathway that is involved in cellular senescence.
They found that senescence associated genes are upregulated in B3 PFC microvessels (2.5-fold increase in senescence-associated genes mRNA).
Of the 40 genes, 11 were significantly upregulated by at least a 2-fold average increase in mRNA expression.
They did not find that plasma senescence-associated protein levels are associated with postmortem severity of AD-related neuropathological changes.