Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s disease (AD), the major form of dementia, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ 1-42 , but not Aβ 1-40 , bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aβ 1-42 . Furthermore, Aβ 1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aβ 1-42 show that the clearance of Aβ 1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ 1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aβ 1-42 in the blood is beneficial to the fight against COVID-19 and AD.
【저자키워드】 COVID-19, ACE2, SARS-CoV-2 spike protein, Alzheimer’s disease, Aβ, 【초록키워드】 SARS-CoV-2, coronavirus, antibody, IL-6, SARS-COV-2 infection, severity, progression, angiotensin-converting enzyme 2, viral entry, Alzheimer’s disease, Dementia, receptor, mechanism, Blood, binding, Evidence, S1 subunit, intravenous, acute respiratory syndrome, Viral protein, severe coronavirus disease, residue, domain, high affinity, trimer, SARS-CoV-2 pseudovirus infection, clearance, Effect, Extracellular, Course, elevated, reducing, the spike protein, prevented, C-terminal, Increasing, 【제목키워드】 spike, Effect, the SARS-CoV-2,