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

Chen, Feng; Chen, Yanting; Wang, Yongxiang; Ke, Qiongwei; Cui, Lili

doi:10.1186/s40035-022-00316-y

Cited by 37 publications

(46 citation statements)

References 233 publications

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“…Some neurological conditions have also been linked to COVID-19 severity [ 201 , 280 , 407 ]. Possible mechanisms include immunosenescence, heightened IFN responses or genetic predisposition to severe COVID-19 (OAS1, APOE ε4 allele) in Alzheimer’s disease [ 350 , 408 , 409 , 410 ], respiratory muscle rigidity and insufficient cough reflex in Parkinson’s disease [ 350 , 411 ], systemic inflammation in epilepsy (with much uncertainty) [ 362 , 412 ] and susceptibility to acute stress in cerebrovascular diseases [ 413 , 414 ]. Increased levels of chronic inflammatory mediators have been observed in several mental disorders (major depressive disorder, bipolar disorder, schizophrenia, and sleeping disorders) [ 415 ].…”

Section: Host Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

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Section: Host Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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“…2 ). It has been demonstrated that SARS-CoV-2 virus could enter the brain, although the routes remain controversial [ 13 , 198 ]. However, very low levels of the SARS-CoV-2 virus are detected in the brains of patients dying from COVID-19 [ 86 , 104 – 106 ].…”

Section: Covid-19 and Admentioning

confidence: 99%

“…This makes AD patients more predisposed to CNS infection and adverse outcomes by the SARS-CoV-2 virus. Therefore, disruption of the ACE/ACE2 balance in AD is postulated as a contributor to the infection and severity of COVID-19 [ 198 ]. Taken together, an in-depth exploration of shared pathogenic mechanisms between AD and COVID-19 is warranted in the future, which could also in turn provide new insights into the identification of biomarkers to track disease progression and treatments of AD.…”

Section: Covid-19 and Admentioning

confidence: 99%

Links between COVID-19 and Parkinson’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms

Huang

Zhang

Tan

et al. 2023

Transl Neurodegener

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The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson’s disease (PD) and Alzheimer’s disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed.

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“…In the periphery, ApoE4 was reported to be associated with an increased risk of type 2 diabetes and cardiovascular disease [8,9]. These ApoE4related diseases have all been implicated in a higher risk of COVID-19 [10][11][12]. Impotently, recent genetic and clinical studies reported the association between the ApoE4 genotype and the risk and severity of COVID-19 disease, but yielded inconsistent results [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway

Chen

et al. 2023

J Transl Med

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Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes. Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression. Results ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18–1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50–2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1–7. Conclusions ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin–angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

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

Cited by 37 publications

References 233 publications

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Links between COVID-19 and Parkinson’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms

ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway

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