The relationship of early- and late-onset Alzheimer’s disease genes with COVID-19

Abstract

Individuals with Alzheimer’s disease and other neurodegenerative diseases have been exposed to excess risk by the COVID-19 pandemic. COVID-19’s main manifestations include high body temperature, dry cough, and exhaustion. Nevertheless, some affected individuals may have an atypical presentation at diagnosis but suffer neurological signs and symptoms as the first disease manifestation. These findings collectively show the neurotropic nature of SARS-CoV-2 virus and its ability to involve the central nervous system. In addition, Alzheimer’s disease and COVID-19 has a number of common risk factors and comorbid conditions including age, sex, hypertension, diabetes, and the expression of APOE ε4. Until now, a plethora of studies have examined the COVID-19 disease but only a few studies has yet examined the relationship of COVID-19 and Alzheimer’s disease as risk factors of each other. This review emphasizes the recently published evidence on the role of the genes of early- or late-onset Alzheimer’s disease in the susceptibility of individuals currently suffering or recovered from COVID-19 to Alzheimer’s disease or in the susceptibility of individuals at risk of or with Alzheimer’s disease to COVID-19 or increased COVID-19 severity and mortality. Furthermore, the present review also draws attention to other uninvestigated early- and late-onset Alzheimer’s disease genes to elucidate the relationship between this multifactorial disease and COVID-19.

microRNA, the Innate-Immune System and SARS-CoV-2

“…Another noteworthy example is that about one third of all COVID-19 patients experience neurological and/or neuropsychiatric symptoms, and a pre-existing diagnosis of Alzheimer’s disease (AD) predicts the highest risk for COVID-19 yet identified, especially among elderly AD patients. ACE2 expression and the density of ACE2 receptors have recently been found to be significantly up-regulated in the temporal lobe neocortex and hippocampal CA1 regions of AD-affected brain, anatomical regions targeted by the inflammatory neuropathology that characterizes AD, and this suggests a significant mechanistic overlap between AD and successful SARS-CoV-2 and other viral infections of the human CNS ( Hill et al., 2009 ; Zhao et al., 2021 ; Choe et al., 2022 ; Lingor et al., 2022 ; Sirin et al., 2022 ; Szabo et al, 2022 ; Wang et al., 2022 ).…”

SARS-CoV-2 Neuroinvasion, Inflammatory Neurodegeneration and Alzheimer's Disease

“…Like many neurotropic viruses with RNA genomes, SARS-CoV-2 has a remarkably broad neuroinvasive capacity and neurons appear to be directly targeted by a particularly virulent infection (Song et al, 2020;Choe et al, 2022;Lukiw et al, 2022). Long-lasting neurological consequences after SARS-CoV-2 infection negatively impacts the brain and CNS in anatomical regions known to be targeted by neurodegenerative events, as is observed throughout all phases of the AD continuum (Lingor et al, 2022;Lukiw et al, 2022;Piekut et al, 2022;Sirin et al, 2022;Szabo et al, 2022). Pre-existing neurological conditions and pathological interactions among the brain, central and peripheral nervous systems (CNS, PNS) and respiratory, cardiovascular and endocrine systems further modulate and/or impact the severity and long-term sequelae of the post-COVID-19 syndrome period (Kallet et al, 2019;Horn et al, 2021;Zuin et al, 2021;Molina-Molina and Hernández-Argudo, 2022;Sanyaolu et al, 2022;Stefanou et al, 2022;Visco et al, 2022).…”

“…Viral and other microbial infections of the brain and CNS have long been known to contribute, amplify or propagate many of the same neuropathological, inflammatory and neurodegenerative changes as is observed over the entire AD continuum (see below; Lingor et al, 2022;Lukiw et al, 2022;Piekut et al, 2022;Sirin et al, 2022;Szabo et al, 2022). Emerging evidence indicates that both DNA and RNA viruses, such as the human double-stranded DNA (dsDNA) Herpes simplex type 1 and 2 (HSV-1, HSV-2), the human cytomegalovirus (HMCV), the Epstein-Barr virus (EBV), and the ssRNA viruses hepatitis C virus (HCV; Herpesviridae), human influenza A viruses (H1N1/H3N2; Orthomyxoviridae), Zika virus (ZIKVs; Flaviviridae), MERS-CoV (Coronaviridae), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Coronaviridae) and a remarkably large number of bacteria of the genus Bacteroides, Borrelia, Chlamydia, Treponema, Porphyromonas, Prevotella, Tannerella, Fusobacterium, Aggregatibacter, Eikenella and Helicobacter, as well as several other eukaryotic parasites (e.g., Toxicara; Toxoplasma) or fungi (Aspergillus; Candida) and others have been implicated in the etiopathology of inflammatory neurodegenerative diseases including AD.…”

“…2021; Vigasova et al, 2021;Choe et al, 2022;Lee et al, 2022;Lingor et al, 2022;Piekut et al, 2022;Protto et al, 2022;Sirin et al, 2022; Figure 1). These neuropathological features become more pronounced over the progression of the AD continuum.…”

“…The normal physiological role of the ACE2R is in the binding and maturation of angiotensin, a circulating peptide hormone derived from its precursor angiotensinogen. Angiotensin functions as a vasoconstrictor and regulates blood flow and blood pressure in the systemic-and neuro-vasculature, the latter an area of the human vascular neurobiology that, besides the limbic system, is targeted in Alzheimer's disease (Carlson and Prusiner, 2021;Xia et al, 2021;Zhao et al, 2021;Lukiw et al, 2022;Sirin et al, 2022;Villa et al, 2022;AD). This 'Opinion paper' will briefly review and comment on our current understanding of SARS-CoV-2 infection of the human CNS and the complex, immediate and long-term contributions of this lethal Betacoronavirus to the altered molecular-genetic and pathophysiological mechanisms that characterizes AD-affected brain.…”