Renin-angiotensin system, or RAS, is a physiological mechanism essential to human body function. The SARS-CoV-2 virus causes overactivation and malfunction of this system. The RAS regulates innate immunity, various microbiota, and the autonomic processes of the kidney, lungs, and heart. The RAS is found in every cell of every tissue and organ in the body, making it ubiquitous. The excess of the hormone angiotensin-2, which overactivates the "deleterious" RAS receptor AT1R, is directly accountable for the pathologies of Covid-19 caused by the malfunctioning. In fact, the AT1R receptor overactivated by abundant angiotensin-2 has a variety of harmful effects on the human body by inducing cellular signaling cascades. The AT1R receptor is pro-hypertensive as it induces blood vessel constriction, pro-inflammatory since it causes a toxic storm of pro-inflammatory cytokines, pro-oxidant because it increases the production of reactive oxygen particles that kill cells, pro-thrombotic because it promotes the formation of clots - or thrombi - that obstruct blood vessels, and pro-angiogenic as it promotes the growth of blood vessels and tumors, pro-hypoxemic because it reduces the load of red blood cells in oxygen and causes desaturation of blood in oxygen, pro-hypoxic because it causes a deficit of oxygen supply to various cells, tissues, and organs, pro-fibrotic because it induces organ fibrosis, pro-hypertrophying because it increases organ volume, and makes nitric oxide fall, affecting inflammatory, immune, and memory phenomena.

Alzheimer's disease is a form of dementia characterized by incapacitating neurological diseases that affect the patients' behavior, memory, thinking, and reasoning skills. Symptomatology usually develops gradually, but in the case of Covid-19 and long Covid it might occur unusually fast. Patients frequently experience memory loss (amnesia), spatial-temporal disorientation, mood and personality disturbances, reduced comprehension and/or inability to solve problems, impairments of written and/or verbal expression (aphasia), and difficulties managing daily tasks. Apraxia is the inability to perform motor movements despite the existence of these "intact" functions, as well as challenges with object recognition despite the existence of "intact" sensory functions (agnosia).

Clinical doctors and pathologists have noted the onset of Alzheimer's disease in a variety of patients, including young adults, following a spontaneous infection with the SARS-CoV-2 virus or even following immunization against Covid-19. A viral infection with SARS-CoV-2 or even an anti-Covid-19 vaccination causes a dysfunction of the RAS, via an excess of the hormone angiotensin-2 normally degraded by the receptor ECA2 (angiotensin-2 converting enzyme) on which the viral or vaccine Spike protein binds and the "deleterious" overactivation of the AT1R receptor of the RAS, at the origin of Covid-19 diseases. The overactivated AT1R receptor is pro-hypertensive, which means it provokes arterial hypertension. This impacts the brain function. Evidently, arterial hypertension has been identified as a significant risk factor for mild to severe neurodegenerative disorders such as dementia and Alzheimer's disease. RAS inhibitors, such as sartans and ACE inhibitors of angiotensin-1 converting enzyme, have been equally shown to improve neurodegenerative diseases and other cognitive dysfunctions. Thus, angiotensin-2, which is found in excess in Covid-19 due to RAS overactivation, promotes the accumulation and deposition of b-amyloid proteins (markers of Alzheimer's disease), impairing brain cell synaptic connections and cognitive functions. Furthermore, the vasoconstrictive effect of a dysfunctional RAS contributes to blood flow limitation in the brain, promoting neurovascular uncoupling, cerebral hypometabolism, and the development of neurological damage.

View the article here: https://www.eurekaselect.com/article/132146

JOURNAL

Infectious Disorders - Drug Targets

DOI

10.2174/1871526523666230529162633

ARTICLE TITLE

Covid-19 And Alzheimer's Disease: The Link Finally Established

ARTICLE PUBLICATION DATE

29-May-2023