Links between COVID-19 and Alzheimer's Disease-What Do We Already Know?

Abstract

Alzheimer's disease (AD) is a life-changing condition whose etiology is explained by several hypotheses. Recently, a new virus contributed to the evidence of viral involvement in AD: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 coronavirus disease. AD was found to be one of the most common COVID-19 comorbidities, and it was found to increase mortality from this disease as well. Moreover, AD patients were observed to present with the distinct clinical features of COVID-19, with delirium being prevalent in this group. The SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is overexpressed in brains with AD, which thus increases the viral invasion. Furthermore, the inhibition of the ACE2 receptor by the SARS-CoV-2 virus may also decrease the brain-derived neurotrophic factor (BDNF), contributing to neurodegeneration. The ApoE ε4 allele, which increases the risk of AD, was found to facilitate the SARS-CoV-2 entry into cells. Furthermore, the neuroinflammation and oxidative stress existing in AD patients enhance the inflammatory response associated with COVID-19. Moreover, pandemic and associated social distancing measures negatively affected the mental health, cognitive function, and neuro-psychiatric symptoms of AD patients. This review comprehensively covers the links between COVID-19 and Alzheimer's disease, including clinical presentation, molecular mechanisms, and the effects of social distancing.

Keywords: Alzheimer’s disease; COVID-19; SARS-CoV-2; neuroinflammation.

Figure 1

A schematic representation of ACE/Ang II/AT1R and ACE2/Ang-(1-7)/Mas axes in AD and SARS-CoV-2 invasion with ACE2 receptor in the spotlight. The ACE2 receptor, through which SARS-CoV-2 enters cells, is upregulated in the brain with AD, which increases viral entry. Moreover, ACE2 transforms Aβ₄₃ into Aβ₄₂, which additionally intensifies the invasion of this virus. Solid arrows represent a transformation of one compound into other, and dotted arrows represent a ligand binding to the receptor. The dotted lines represent an effect caused by activation of the receptor and red lines represent inhibition. Abbreviations: Aβ—amyloid beta; ACE—angiotensin converting enzyme; AD—Alzheimer’s disease; Ang—angiotensin; ARBs—angiotensin receptor blockers; AT₁R—angiotensin II type 1 receptor; BDNF—brain-derived neurotrophic factor; MasR – Mas receptor.