The COVID-19 pandemic and Alzheimer's disease: mutual risks and mechanisms

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer's disease (AD) are more susceptible to SARS-CoV-2 infection and prone to severe clinical outcomes. Recent studies have revealed some common risk factors for AD and COVID-19. An understanding of the association between COVID-19 and AD and the potential related mechanisms may lead to the development of novel approaches to treating both diseases. In the present review, we first summarize the mechanisms by which SARS-CoV-2 invades the central nervous system (CNS) and then discuss the associations and potential shared key factors between COVID-19 and AD, with a focus on the ACE2 receptor, apolipoprotein E (APOE) genotype, age, and neuroinflammation.