Fig. 3
From: The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms
APOE4 contributes to increased susceptibility to COVID-19. a APOE4 was shown to increase the infectivity of SARS-CoV-2 in iPSC-derived neurons and astrocytes. b APOE4 has been reported to be associated with increased BBB permeability. c ApoE4 is related to increased production of proinflammatory cytokines by macrophages in the periphery and by microglial cells in the CNS. d Compared to AD patients presenting the APOE ε3/ε3 genotype, AD patients with the ε4/ε4 genotype display decreased expression of several antiviral defence genes, such as IFITM2, IFITM3, IFNAR1 and LY6E. e Individuals carrying the ε4 allele exhibit elevated intracellular and circulating cholesterol levels, and a high level of cellular cholesterol may facilitate SARS-CoV-2 infection. f APOE4 is a risk factor for several cardiovascular and neurological diseases, and individuals with these pre-existing comorbidities are more vulnerable to infection and poor clinical outcomes. Thus, individuals with the APOE4 genotype are more susceptible to SARS-CoV-2 infection, which may lead to neurodegeneration