Alzheimer's Disease and SARS-CoV-2: Pathophysiological Analysis and Social Context

Abstract

The COVID-19 pandemic has proven to be a challenge for healthcare systems, especially in terms of the care of patients with Alzheimer's disease (AD). Age is one of the major risk factors for severe forms of COVID-19, most probably due to the presence of comorbidities and inflammations. It is known that SARS-CoV-2 invades nerve endings and olfactory nerves through the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction triggers an inflammatory cascade that results in cognitive impairment. In turn, the isoform of apolipoprotein-E4 (APOE-4ε) in AD is a risk factor for increased neuroinflammation through microglia activation, increased oxidative stress, and neurodegeneration. AD and SARS-CoV-2 are associated with increases in levels of inflammatory markers, as well as increases in levels of APOE-4ε, ACE2 and oxidative stress. Thus, there is a synergistic relationship between AD and SARS-CoV-2. In addition, the social isolation and other health measures resulting from the pandemic have led to a higher level of anxiety and depression among AD patients, a situation which may lead to a decline in cognitive function. Therefore, there is a need to develop strategies for keeping the patient calm but active.

Keywords: Alzheimer’s disease; COVID-19; SARS-CoV-2; inflammation; neurodegeneration; social behavior; social support.

Figure 1

(A) APOE 4 is increased in patients with AD and with COVID-19. This increases neuroinflammation which damages the BBB, allowing the passage of viral particles such as SARS that can be distributed to mechanoreceptors and chemoreceptors in the lungs and airways. (B) AD patients have increased expression of ACE2, which increases the probability that SARS CoV-2 binds to its receptor in the respiratory epithelium, lung parenchyma, cardiomyocytes, vascular endothelium, cardiorespiratory neurons of the brainstem, motor cortex and raphe nucleus. (C) On the other hand, in patients with AD, the accumulation of amyloid beta plaques forms fibrils, allowing the deposition of viral particles, which increases the possibility of developing severe stages due to COVID 19 and higher mortality.

Figure 2

Activities to reduce stress during the pandemic. The design of the image is own creation, but the information of the image was based on recommendations to develop activities in the house of the Alzheimer’s Association and in the article of Bacsu [63,67].