Severe COVID-19 in Alzheimer's disease: APOE4's fault again?
Nian Xiong1, Martin R Schiller2, Jingwen Li1
1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
Insights
The apolipoprotein E4 (APOE4) gene isoform increases Alzheimer's disease (AD) patients' risk for severe COVID-19. APOE4 influences infectivity, disease severity, and exposure risk, highlighting its role in COVID-19 outcomes.
Area of Science:
- Neuroscience
- Infectious Diseases
- Genetics
Background:
- Alzheimer's disease (AD) patients face heightened risks during the COVID-19 pandemic due to elevated infection and mortality rates.
- Identifying underlying risk factors and biomarkers is crucial for developing evidence-based healthcare strategies for AD patients affected by COVID-19.
Discussion:
- The apolipoprotein E (APOE) gene, particularly the APOE4 isoform, is implicated in increased susceptibility and severity of COVID-19 in AD patients.
- Mechanistic evidence links APOE4 to heightened SARS-CoV-2 infectivity at the cellular level and association with severe COVID-19 at the genetic level.
- Network analysis reveals connections between APOE and key COVID-19 risk factors, including ACE2, TMPRSS2, NRP1, and LZTFL1, at the pathway level.
Key Insights:
- APOE4 may increase coronavirus exposure risk in individuals with dementia, contributing to higher COVID-19 incidence.
- The APOE4 isoform appears to play a multifaceted role, potentially driving both infection susceptibility and disease severity in the context of COVID-19.
- Understanding APOE's role is vital for targeted interventions and improved healthcare for vulnerable Alzheimer's disease populations.
Outlook:
- Further research into APOE's specific molecular mechanisms in COVID-19 pathogenesis is warranted.
- Development of biomarkers based on APOE status could enable personalized risk assessment and management strategies for AD patients.
- Investigating therapeutic strategies targeting APOE pathways may mitigate COVID-19 risks in Alzheimer's disease populations.
Abstract:
Challenges have been recognized in healthcare of patients with Alzheimer's disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE with COVID-19 risk factors such as ACE2, TMPRSS2, NRP1, and LZTFL1; at a behavioral level, APOE4-associated dementia may increase the exposure to coronavirus infection which causes COVID-19. Thus, APOE4 could exert multiple actions for high infection and mortality rates of the patients, or generally, with COVID-19.
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