tetano
Editor, Senior Moderator
Mol Psychiatry
. 2025 Apr 6.
doi: 10.1038/s41380-025-03006-z. Online ahead of print. Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer's disease and COVID-19
Sijie Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Jingyi Sun[SUP] #[/SUP][SUP] 3 [/SUP], He Li[SUP] 4 [/SUP], Zhifa Han[SUP] 5 [/SUP], Tao Wang[SUP] 6 [/SUP], Shan Gao[SUP] 2 [/SUP], Ping Zhu[SUP] 2 [/SUP], Yan Chen[SUP] 7 [/SUP], Peiguang Yan[SUP] 8 [/SUP], Mingxin Wang[SUP] 9 [/SUP], Guiyou Liu[SUP] 10 11 12 [/SUP]
Affiliations
It is known that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19). It is widely reported that Alzheimer's disease (AD) is associated with the highest risk of COVID-19 infection, hospitalization and mortality. However, it remains largely unclear about the link between AD and COVID-19. ACE2 is an entry receptor for SARS-CoV-2. We consider that there may be a link between AD and COVID-19 through the expression of ACE2. Here, we summarize recent findings about the ACE2 expression especially in AD and COVID-19, and shows that (1) ACE2 shows mRNA and protein expression in human brain tissues, especially in neurons and non-neuron cells; (2) low ACE2 mRNA and protein expression are sufficient for SARS-CoV-2 entry into the human brain through the neural route (olfactory and/or vagal) and the hematogenous route; (3) SARS-CoV-2 RNA and protein were detected in brains of COVID-19 patients; (4) SARS-CoV-2 infects and replicates in human brain dependent on ACE2; (5) SARS-CoV-2 viral RNA load shows a positive association with ACE2 mRNA levels and COVID-19 severity; (6) ACE2 shows increased expression in AD compared with controls in human brain; (7) ACE2 shows increased expression in COVID-19 compared with controls in human brain; (8) ACE2 expression levels affect COVID-19 outcomes. Together, ACE2 shows significantly increased mRNA and protein expression in AD compared with controls in human brain. Consequently, the increased expression of ACE2 would facilitate infection with SARS-CoV-2, and play a role in the context of COVID-19. These findings suggest that the expression of ACE2 may partly explain the link of AD with COVID-19 infection, hospitalization and mortality.
. 2025 Apr 6.
doi: 10.1038/s41380-025-03006-z. Online ahead of print. Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer's disease and COVID-19
Sijie Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Jingyi Sun[SUP] #[/SUP][SUP] 3 [/SUP], He Li[SUP] 4 [/SUP], Zhifa Han[SUP] 5 [/SUP], Tao Wang[SUP] 6 [/SUP], Shan Gao[SUP] 2 [/SUP], Ping Zhu[SUP] 2 [/SUP], Yan Chen[SUP] 7 [/SUP], Peiguang Yan[SUP] 8 [/SUP], Mingxin Wang[SUP] 9 [/SUP], Guiyou Liu[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 40189700
- DOI: 10.1038/s41380-025-03006-z
It is known that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19). It is widely reported that Alzheimer's disease (AD) is associated with the highest risk of COVID-19 infection, hospitalization and mortality. However, it remains largely unclear about the link between AD and COVID-19. ACE2 is an entry receptor for SARS-CoV-2. We consider that there may be a link between AD and COVID-19 through the expression of ACE2. Here, we summarize recent findings about the ACE2 expression especially in AD and COVID-19, and shows that (1) ACE2 shows mRNA and protein expression in human brain tissues, especially in neurons and non-neuron cells; (2) low ACE2 mRNA and protein expression are sufficient for SARS-CoV-2 entry into the human brain through the neural route (olfactory and/or vagal) and the hematogenous route; (3) SARS-CoV-2 RNA and protein were detected in brains of COVID-19 patients; (4) SARS-CoV-2 infects and replicates in human brain dependent on ACE2; (5) SARS-CoV-2 viral RNA load shows a positive association with ACE2 mRNA levels and COVID-19 severity; (6) ACE2 shows increased expression in AD compared with controls in human brain; (7) ACE2 shows increased expression in COVID-19 compared with controls in human brain; (8) ACE2 expression levels affect COVID-19 outcomes. Together, ACE2 shows significantly increased mRNA and protein expression in AD compared with controls in human brain. Consequently, the increased expression of ACE2 would facilitate infection with SARS-CoV-2, and play a role in the context of COVID-19. These findings suggest that the expression of ACE2 may partly explain the link of AD with COVID-19 infection, hospitalization and mortality.