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Advanced Neurology COVID-19 and neurodegenerative diseases

6. AD olfactory epithelium. This finding suggests an unlikely
association of direct infection of the virus into the brain.
6.1. Prevalence and etiology
Activation of microglia and astrocytes to release
Based on global estimates, 44 million people live with proinflammatory cytokines (e.g., IL-6, IL-1, IL-12, and
dementia, with Alzheimer’s dementia, which account for TNF-α) lays grounds for significant pathogenesis of AD,
50 – 75% of all dementias, standing as the chief cause. The that is, through neuroinflammation. IL-6, playing a central
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number of people with dementia is projected to increase to role in cytokine storm of COVID-19, is also implicated in
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131.5 million by 2050. 39 neuroinflammatory disorders like AD. Another cytokine
Familial AD is a rare early-onset disease occurring involved in the pathogenesis of COVID-19, IL-1, is
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due to mutations in genes such as the amyloid precursor responsible for the severity of memory loss in AD patients.
protein (APP) gene and presenilin 1/2 (PSEN1/2), which Therefore, the pre-existing neuroinflammation aggravates
are involved in Aβ metabolism. In contrast, the far more the cytokine storm of COVID-19 in AD patients. On the
common, late-onset, and sporadic form of AD has an contrary, researchers postulate that these cytokines might
under-defined etiology and is believed to be caused by an also increase the vulnerability of severe COVID-19 patients
interaction between environmental, lifestyle, and genetic to dementia in the later stages of their lives. 50
factors. Various comorbidities such as type-2 diabetes Gal-3, which is a β-galactoside-binding protein, is
mellitus, vascular diseases, immune system dysfunction, not only involved in the exaggerated inflammation and
and traumatic brain damage have been identified in fibrosis of the lungs in severely ill COVID-19 patients
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association with AD. Senile plaques, neurofibrillary tangles but also associated with cognitive impairment in patients
(NFTs), and neuroinflammation induced by Aβ aggregates with AD. Thus, Gal-3 shows immense promise both as
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all contribute to neuronal dysfunction in such patients. 41 an inflammatory marker and a therapeutic target for the
6.2. Influence of COVID-19 on AD management of COVID-19 in patients with AD. The
high level of VCAM-1, which is an endothelial marker
Aging has been recognized as the supreme risk factor for responsible for vasculitis caused by COVID-19, is also
AD as findings estimate a 19% increase in prevalence in eminent in AD patients. Interestingly, VCAM-1 indicates
individuals between 75 and 84 years of age and 30 – 35% for the severity of COVID-19 and reflects the extent of
those older than 85 years. Aging causes elevated oxidative dementia in AD patients. All above-stated evidence
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stress, disruption of BBB, and epigenetic changes, thus corroborates the fact that AD is the prime risk factor for
rendering aging a principal risk factor for not only AD but mortality among COVID-19 patients. The survival rate
also COVID-19. was found to be significantly lower in COVID-19 patients
APOE genes encode proteins that are responsible for with AD compared to those without AD. The claim was
the removal of Aβ protein, but the highly predisposing also supported by the low number of T regulatory cells
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genotype for AD, APOEε4, has been proven to be less failing to control the infection in patients with AD. 53
efficacious in Aβ protein clearance. A decline in the Further, the mortality rate was observed to be higher
expression of antiviral defense genes has been reported, in AD patients living in care homes compared to those
predisposing the carriers of these genes to COVID-19. living in residential homes. This can be accredited to the
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Moreover, increased expression of this genotype is increased circulating viral load in the premises of care
associated with obesity and cardiovascular diseases, which homes, which leads to the rapid transmission of the virus.
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are known risk factors for COVID-19. The SARS-CoV-2 A cohort study by Li et al. comparing the duration of
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virus gains entry through the olfactory epithelium and hospitalization in AD and non-AD COVID-19 patients
binds with its S protein to the ACE2 receptor present on the with mild pneumonia demonstrated a surprisingly shorter
surface of neurons, glial cells, and capillary endothelium. It duration of hospital stay in the former group of patients.
has been observed that a noteworthy rise in the levels of This unexpected outcome is supported by the finding that
ACE2 receptors in the brain tissues of AD patients helps the AD patients took up early medical intervention to
drive an increased invasion by this neurotropic virus. An address the COVID-19 symptoms before engaging with
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extensive study by Zhou et al. examining the expression health services, highlighting the importance of timely
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of key entry factors of COVID-19 – ACE2, TMPRSS2, access to apt treatment. The study did not observe a
FURIN, and NRP1 – in brain tissue of both healthy and significant difference in the severity of pneumonia between
AD patients found that these factors across 13 sites of the these two groups of patients. The current treatment for AD
brain including the cerebral cortex and hippocampus are encompasses anticholinesterase drugs such as donepezil,
possible targets for the virus when entering through the rivastigmine, and galantamine. The latter has been proven
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Volume 3 Issue 1 (2024) 6 https://doi.org/10.36922/an.2200