COVID-19 and Alzheimer’s Disease: A Literature Review
Abstract
:1. Introduction
2. Overview on Alzheimer’s Disease
2.1. Causes of Alzheimer’s Disease
- Beta-amyloid plaque production: elevated cholesterol levels in the blood cause the creation of beta-amyloid plaques. When proteins cluster together, they form a hard, insoluble plaque. Plaque builds up between neurons in the brain, inhibiting cell communication and function. These cells eventually die as a result of this. When brain cells deteriorate and die, they lose their ability to process, store, and retrieve data. As a result, one of Alzheimer’s symptoms is memory loss [12]. AD is associated with hyperphosphorylation of tau protein and accumulation of amyloid-β peptide in the brain [13].
- Multi-pathogen infections: the interaction of several potential pathogens with neurodegeneration and neuroinflammation in AD has been reported [13,14]. Various pathogens, including viruses (Herpes simplex virus type 1) and oral infectious pathogens, especially periodontal infections caused by Porphyromonas gingivalis, a key pathogen in chronic periodontitis, was found in AD cases. However, other bacteria, such as Helicobacter pylori, which is associated with chronic gastric diseases, and Chlamydophila pneumoniae, which is implicated in chronic and lower-respiratory-tract diseases, also to play a role in AD [14].
- Neurofibrillary tangles: Tau proteins are disrupted by an increase in enzymes called tau kinases. They clump together and create neurofibrillary tangles as their structure changes. The tangles injure brain cells by disrupting cell communication [15].
- Blood flow deficiency: A lack of blood flow to the brain prevents the transfer all of the necessary nutrients to the cells. Blood clots, on the other hand, harm blood vessels. As a result, the memory-related areas of the brain, such as the amygdala and the hippocampus, do not receive enough blood, and this leads to the deterioration of the brain function [16].
2.2. Types of AD
- The most frequent type of AD is late-onset, which manifests symptoms in the mid-60 s. This type of AD is not produced by one gene only. One gene, however, could be a risk factor. The apolipoprotein E gene (APOE) has one allele (a variant form of a gene) that raises a person’s risk of developing this type of Alzheimer’s [19].
3. Overview on COVID-19 Disease
4. The Impact of COVID-19 on Alzheimer’s Disease
4.1. Direct Neurological Consequences of COVID-19 on People with Alzheimer’s Disease
- “SARS-COV-2” enters the brain via the olfactory system. In fact, loss of smell is common in COVID-19 infection. MRI hypersignals of the olfactory epithelial cortex indicate infection especially with the presence of ACE2 receptors and TMPRSS2 in the olfactory epithelium [36]. The virus could enter by nerve terminals and spread into the brain as described by Dubé et al. [37]. Therefore, it is not evident that the virus reaches the olfactory neurons in this manner.
- Via blood-brain barrier (BBB): the virus reaches the brain by infecting the endothelial cells [35]. The presence of ACE2 receptors, other putative “SARS-COV-2” receptors, and inflammatory cytokines like interleukin (IL)-6, IL-1b, tumor necrosis factor (TNF), and IL-17 disrupt the BBB and may facilitate the entry of the virus to the brain endothelial cells [38]. The presence of pre-existing neurological disease or comorbidities increases the permeability of BBB.
- Infiltration with infection immune cells: infected immune cells can transfer virus to the brain. It is unclear if “SARS-COV-2” can enter immune cells for infection and transport to the CNS [39]. Chen et al. demonstrated the presence of “SARS-COV-2” nucleocapsid proteins in CD68 lymphocytes and macrophage; nonetheless, it is not clear whether it is the normal process of phagocytosis or infected cells [40]. In addition, many cerebral autopsies reveal a lack of immune cells [41].
4.2. Indirect Consequences of COVID-19 on People with Alzheimer’s Disease
5. Management Strategies
6. Future Perspective
7. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
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Hardan, L.; Filtchev, D.; Kassem, R.; Bourgi, R.; Lukomska-Szymanska, M.; Tarhini, H.; Salloum-Yared, F.; Mancino, D.; Kharouf, N.; Haikel, Y. COVID-19 and Alzheimer’s Disease: A Literature Review. Medicina 2021, 57, 1159. https://doi.org/10.3390/medicina57111159
Hardan L, Filtchev D, Kassem R, Bourgi R, Lukomska-Szymanska M, Tarhini H, Salloum-Yared F, Mancino D, Kharouf N, Haikel Y. COVID-19 and Alzheimer’s Disease: A Literature Review. Medicina. 2021; 57(11):1159. https://doi.org/10.3390/medicina57111159
Chicago/Turabian StyleHardan, Louis, Dimitar Filtchev, Ratiba Kassem, Rim Bourgi, Monika Lukomska-Szymanska, Hassan Tarhini, Fouad Salloum-Yared, Davide Mancino, Naji Kharouf, and Youssef Haikel. 2021. "COVID-19 and Alzheimer’s Disease: A Literature Review" Medicina 57, no. 11: 1159. https://doi.org/10.3390/medicina57111159