Research has shown that there is a link between prior infection with certain viruses and the development of neurodegenerative diseases later in life. This extends to AD, where infection with viruses such as
herpes simplex virus (HSV),
varicella zoster virus (VZV), or
Epstein-Barr virus (EBV), among others, increases risk of developing AD. In a study of 6,245,282 patients, it was observed that cognitively normal individuals over 65 are at an increased risk of a new dementia diagnosis following COVID-19 infection. Moreover, COVID-19 has been shown to potentially exacerbate the progression of existing AD, leading to increased research interest into the interaction between the two diseases The RAS system involves the proteins
angiotensinogen,
renin, and
ACE, all of which are present in the brain. Renin is an enzyme that cleaves angiotensinogen into angiotensin I (Ang I), while ACE converts Ang I into Ang II. Some studies have found a link between increased ACE2 in the brain and AD, however this remains controversial. Additionally, ACE2 has been shown to convert toxic Aβ43 into protective Aβ40, decreasing amyloid burden.
NLRP3 is one protein in this family that is involved in the body's response to
bacteria,
fungi, and
viruses. From here, the NLRP3 inflammasome will cleave inactive pro-inflammatory proteins such as
pro-interleukin(IL)-1β and
pro-IL-18 to their active forms, which continue to promote inflammation. The expression of genes related to inflammasome activation were shown to be increased in AD, while stimulation of immune cells with Aβ42 can directly activate it. It is through this mechanism that SARS-CoV-2 is thought to increase deposition of toxic Aβ42 and hyperphosphorylated tau, worsening AD pathology. The subsequent increase in inflammatory
cytokines can further lead to
neurodegeneration and cognitive impairment.
Cytokines Cytokines are cellular messages given off by immune cells and different tissues that can help promote or stop an immune response. These molecules are produced as a part of the normal immune response and are greatly increased due to SARS-CoV-2 infection. However,
uncontrolled cytokine release can be detrimental or even fatal, especially in cases of severe COVID-19. In addition to their role in viral infections, cytokines are highly abundant in the brains of AD patients. While these cytokines are essential in mounting a response to COVID-19 infection, they may consequently drive neurodegeneration in AD patients.
Social factors influencing worsening of AD symptoms The onset of the COVID-19 pandemic brought many public health measures into the spotlight, such as
lockdowns and mandatory face mask use. Social isolation of AD patients due to COVID-related lockdowns has been shown to worsen the
psychiatric symptoms of AD, including depression, agitation, and hallucinations. This partially is thought to arise from lack of socialization and mental stimulation associated with caregiver programs and social interaction. Exercise is associated with increased blood flow to the brain and improved cognitive function. Exercise has also been shown to potentially improve psychiatric symptoms and slow the decline in the ability to perform daily tasks in AD patients. Additionally, AD patients often require a sense of familiarity in their surroundings and those they interact with. Despite the need for familiarity, AD patients often have
trouble recognizing faces. Mandatory face masking, while essential to prevent viral spread, can further impair facial recognition in AD. This has been proposed to contribute to distress and declining mental health in AD patients. == References ==