The viral hypothesis in Alzheimer’s disease: SARS-CoV-2 on the cusp

Abstract

Increasing evidence highlights that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has long-term effects on cognitive function, which may cause neurodegenerative diseases like Alzheimer’s disease (AD) in the future. We performed an analysis of a possible link between SARS-CoV-2 infection and AD risk and proposed several hypotheses for its possible mechanism, including systemic inflammation, neuroinflammation, vascular endothelial injury, direct viral infection, and abnormal amyloid precursor protein metabolism. The purpose of this review is to highlight the impact of infection with SASR-CoV-2 on the future risk of AD, to provide recommendations on medical strategies during the pandemic, and to propose strategies to address the risk of AD induced by SASR-CoV-2. We call for the establishment of a follow-up system for survivors to help researchers better understand the occurrence, natural history, and optimal management of SARS-CoV-2-related AD and prepare for the future.

The Contribution of Microglia and Brain-Infiltrating Macrophages to the Pathogenesis of Neuroinflammatory and Neurodegenerative Diseases during TMEV Infection of the Central Nervous System

“…The CNS has a unique and complex structure with a restricted regeneration capacity. The perturbation of the CNS homeostasis, induction of neuroinflammation, neuronal damage, and neuron degeneration often occur as a result of a CNS viral infection and are closely associated with the development of neuroinflammatory and neurodegenerative diseases such as multiple sclerosis (MS) [ 6 , 7 , 8 , 9 , 10 , 11 ], Alzheimer’s [ 10 , 12 , 13 ], epilepsy [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], and others [ 26 , 27 , 28 , 29 , 30 ]. In fact, viral infections are known or suspected to play a role in the onset and progression of various neurological disorders.…”

“…The CNS has a unique and complex structure with a restricted regeneration capacity. The perturbation of the CNS homeostasis, induction of neuroinflammation, neuronal damage, and neuron degeneration often occur as a result of a CNS viral infection and are closely associated with the development of neuroinflammatory and neurodegenerative diseases such as multiple damage, and neuron degeneration often occur as a result of a CNS viral infection and are closely associated with the development of neuroinflammatory and neurodegenerative diseases such as multiple sclerosis (MS) [6][7][8][9][10][11], Alzheimer's [10,12,13], epilepsy [14][15][16][17][18][19][20][21][22][23][24][25], and others [26][27][28][29][30]. In fact, viral infections are known or suspected to play a role in the onset and progression of various neurological disorders.…”

Unlocking the Protective Potential of Upper Respiratory Infection Treatment Histories against Alzheimer’s Disease: A Korean Adult Population Study

“…While the acute symptoms of URIs are typically mild and transient, mounting evidence suggests that they may have more profound and long-lasting effects on human health than previously recognized [6]. Emerging research has implicated inflammatory responses triggered by viral and bacterial pathogens during URIs as potential contributors to neuroinflammation and neuronal damage, processes known to be central in AD pathogenesis [7,8]. Intriguingly, a growing body of research has uncovered connections between bacteria like Chlamydia pneumoniae and viruses like influenza virus, herpes simplex virus, adenoviruses, poliovirus, measles virus, cytomegalovirus, severe acute respiratory syndrome coronavirus 2 (COVID- 19), and AD pathology [7,[9][10][11], demonstrating that hippocampal cells are highly susceptible to infection by several viruses [12].…”

Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease

“…During the period of 2020–2021, the number of deaths from stroke, cardiovascular disease, and human immunodeficiency virus decreased, whereas the number of people who died from AD increased more than 145% [ 2 ]. There is growing evidence that such a significant increase in mortality from AD may be associated with the COVID-19 pandemic in 2020 and 2021 [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. COVID-19 is primarily known as a severe acute respiratory disease caused by the SARS-CoV-2 virus, but it also affects the central nervous system (CNS) and other organs [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…However, despite considerable evidence that there is a relationship between COVID-19 and AD, it remains unclear if the SARS-CoV-2 virus itself causes AD and/or if the SARS-CoV-2 infection exacerbates existing AD. The virus hypothesis for AD has been proposed for decades, and despite supportive evidence, virus etiology of AD is still controversial [ 7 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. On the one hand, many clinical observations indicate an increased risk for COVID-19 in people with AD [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”