Association of apolipoprotein E4 to the number of cerebral microbleeds in patients recovered from COVID-19

Background: COVID-19 has been associated with cerebral microbleeds (CMB). Previously, an association of ApoE4 with COVID-19 severity and CMBs in autopsy was found. In this study, we investigated if carrying the Apoe4 allele relates to the number of CMBs in magnetic resonance imaging (MRI) in patients recovered from COVID-19. Material(s) and Method(s): Adult patients recovered from COVID-19 and a control group without a history of COVID-19 was recruited. Exclusion criteria were major neurologic disease, developmental disability or pregnancy. The participants underwent brain MRI 6 months after infection, and a blinded neuroradiologist analyzed the findings. ApoE was genotyped using a microarray. Statistical analysis was performed using the statistical software R. A negative binomial model was chosen based on the distribution of CMBs. Result(s): Of the 216 subjects that underwent MRI, 168 consented to genetic testing, additionally 2 patients were excluded due to extensive CMBs and 1 due to diffuse axonal injury. We included 113 COVID-19 patients (49 ICU-treated, 29 ward-treated and 35 home-isolated) and 52 controls. The most prevalent comorbidities were hypertension, asthma and diabetes. CMBs was found in 47 subjects, with the number of CMBs ranging from 0 to 26. The ApoeE4 allele was carried by 37%, equally distributed among the groups. After adjustment, age (aRR = 1.06, p = 0.007) and COVID-19 (aRR = 2.59, p = 0.038) were independently associated with CMBs. The ApoE4 allele (aRR = 2.16, p = 0.07, CI = 0.94-5.10) was not significant. Conclusion(s): Age and previous COVID-19, but not possession of the ApoeE4 allele, were independently associated with the number of CMBs.

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of ß-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.

COVID-19 Mortality and the Cytokine Storm: An Added Value for APOE Genotyping

The new COVID-19 presents some comorbidities, such as obesity, Alzheimer's, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the para-doxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipopro-tein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proin-flammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like beta-amyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications;and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.Copyright © 2022 Bentham Science Publishers.

Relation between apolipoprotein e in alzheimer's disease and sars-cov-2 and their treatment strategy: A review.

COVID-19, which primarily affects the pulmonary system, turned out to be a global pandemic, whereas the effects on other systems are still unknown. SARS-CoV-2, binds to angiotensin-converting enzyme 2 (ACE2) receptors in the lungs, causing pneumonia-like symptoms. The same ACE receptors are also present in organs other than the lungs. Therefore, there is a need to study the impact of coronavirus on other human body organs. Recently, UK Biobank reports on the genetic risk factor of the virus attack. A double mutation in the apolipoprotein E (APOE4) allele has shown a significant role in COVID-19. The same APOE4 mutation has already been proven to hold a key role in developing early-onset Alzheimer's disease (EOAD). Despite this data, Alzheimer's disease is believed to be a comorbidity of COVID-19. Previous virus attacks on the same viral family, Coronaviridae, produced neurological effects like neurodegeneration, neuronal inflammation, and other central nervous system-related dysfunctions. Since the long-term implications of COVID-19 are unknown, more research into the impact of the virus on the central nervous system is needed. Both COVID-19 and AD share a common genetic factor, so that AD patients may have a greater risk of SARS-CoV-2. Here, in this review, we have briefly discussed the role of APOE4 in the pathogenesis of AD and SARS-CoV-2, along with their treatment strategy, current scenario, and possible future directions.

Lung health after covid . . . and other stories

Among 3000 people with hypertension inadequately controlled by medication, who were treated with renal denervation, there were sustained reductions in systolic blood pressure and fewer major cardiovascular events over 36 months of follow-up (J Am Coll Cardiol doi:10.1016/j.jacc.2022.08.802). PACE labels Ten worksite cafeterias in England were randomised in the order in which they introduced labels containing information about physical activity calorie equivalents (PACE labels) on selected food and drinks. Experiments in transgenic mice and in cell culture now link the APOE gene with faulty lipid processing in oligodendrocytes.

Cholesterol and obesity: A marker for Alzheimer's disease

Modern lifestyle and fast-food consumption nature increase the cholesterol consumption and deposition in our body. It is becoming one of the key risk factors in AD development. Several genes and receptors play crucial roles in such developments. Consumption of high-fat diet and absence of physical activity can lead to obesity. Higher BMI is the indicator of obesity. Higher BMI accelerates AD development due to brain atrophy, neuroinflammation, and oxidative stress in the hippocampus. Obesity in childhood and adolescence leads to dementia and AD in later life. COVID harmfully affects Alzheimer's patients, and it is also reported that COVID related dementia and neurodegeneration is one of the prominent post-COVID complications. This review summarises the role of cholesterol in Alzheimer's disease development and the importance of genes, receptors, and diet behind this.

Forthcoming Articles

B Neurological and neurophysiological changes associated with SARS-CoV-2 infection: New observations, new mechanisms b Muhammed Ali Haidar, Hussam Jourdi, Zeinab Haj Hassan, Ohanes Ashekyan, Manal Fardoun, Mark Wehbe, Ghassan Dbaibo, Hassan Zaraket, Ali Eid, & Firas Kobeissy B Circular RNAs in the brain: A possible role in memory? b Esmi Zajaczkowski & Timothy Bredy B Giacomo Balla: A painter in the context of neuroscience b Letizia Maria Cupini & Paolo Calabresi B Blood-brain barrier (BBB) disruption: A common driver of central nervous system (CNS) diseases b Berta Segura-Collar, Pablo Mata-Martinez, Aurelio Hernández-Laín, Pilar Sanchez-Gomez, & Ricardo Gargini B The neurobiology of pathological fatigue: New models, new questions b Annapoorna Kuppuswamy B How and why the cerebellum recodes input: An alternative to machine learning b Mike Gilbert & Chris Miall B Role of adaptive immune and impacts of risk factors on adaptive immune in Alzheimer's disease: Are immunotherapies effective or off-target?. [Extracted from the article] Copyright of Neuroscientist is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Association of Apolipoprotein e polymorphism with SARS-CoV-2 infection.

Coronavirus 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The disease resulted in global morbidity and mortality that led to considering as pandemic. The human body response to COVID-19 infection was massively different from being asymptomatic to developing severe symptoms. Host genetic factors are thought to be one of the reasons for these disparities in body responses. Few studies have suggested that Apolipoprotein Epsilon (Apo E) is a candidate gene for playing roles in the development of the disease symptoms. This work aims to find an association between different Apo E genotypes and alleles to COVID-19 infection comparing a general population and a group of COVID-19 patients. For the first time, the results found that Apo E4 is associated with COVID-19 disease in a Kurdish population of Iraq. Further study is required to reveal this association in different ethnic backgrounds all over the world.

Immunoinflammatory role of apolipoprotein E4 in malnutrition and enteric infections and the increased risk for chronic diseases under adverse environments.

Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments. In this review, recent findings are summarized of apoE's effects on intestinal function in health and disease and the role of APOE4 in protecting against infection and malnutrition in children living in unfavorable settings, where poor sanitation and hygiene prevail, is highlighted. The potential impact of APOE4 on later development also is discussed and gaps in knowledge are identified that need to be addressed to protect children's development under adverse environments.

Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer's Disease (AD); Underwhelming Evidence against.

This review describes investigations of specific topics that lie within the general subject of HSV1's role in AD/dementia, published in the last couple of years. They include studies on the following: relationship of HSV1 to AD using neural stem cells; the apparent protective effects of treatment of HSV1 infection or of VZV infection with antivirals prior to the onset of dementia; the putative involvement of VZV in AD/dementia; the possible role of human herpes virus 6 (HHV6) in AD; the seemingly reduced risk of dementia after vaccination with diverse types of vaccine, and the association shown in some vaccine studies with reduced frequency of HSV1 reactivation; anti-HSV serum antibodies supporting the linkage of HSV1 in brain with AD in APOE-ε4 carriers, and the association between APOE and cognition, and association of APOE and infection with AD/dementia. The conclusions are that there is now overwhelming evidence for HSV1's role-probably causal-in AD, when it is present in brain of APOE-ε4 carriers, and that further investigations should be made on possible prevention of the disease by vaccination, or by prolonged antiviral treatment of HSV1 infection in APOE-ε4 carriers, before disease onset.

Could COVID-19 anosmia and olfactory dysfunction trigger an increased risk of future dementia in patients with ApoE4?

The association of the coronavirus disease 2019 (COVID-19) with significant neurological and neuropsychiatric complications has been increasingly reported, both during the acute illness and in its aftermath. However, due to the short duration of patient follow up until now, it is not clear whether this infection will be associated with longer-term neurological and/or neuropsychiatric sequelae. In particular, the question of whether COVID-19 will be associated with an increased risk and rate of future dementia remains open and subject to speculation. During the course of the COVID-19 pandemic, an increasing number of patients have reported sudden anosmia or other olfactory dysfunction as concurrent symptoms. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reach the brain via the olfactory nerve or an upper nasal trancribrial route is an interesting working hypothesis. Among the identified genetic risk factors for Late-onset Alzheimer's disease (LOAD), Apo E4 is one of the strongest and most frequent. People carrying one or two copies of the e4 allele of Apo E4 have significant odor recognition deficits in comparison to those not carrying this haplotype. The hypothesis invoked in this paper is that anosmia/olfactory dysfunctions induced by SARS-CoV-2 may cause an increased a risk of future neurodegenerative dementia in ApoE4 carriers, and that this risk would be higher than in Apo E4 carriers affected by anosmia not induced by SARS-CoV-2. This would be associated with virus-induced chronic modifications in the central nervous system. It is proposed that COVID-19 patients with anosmia and no other serious symptoms should be followed up as part of specifically designed and approved studies in order to identify the early stages of dementia (especially LOAD and Dementia with Lewy Bodies), thereby improving our knowledge of the mechanisms involved in pre-cognitive stages of neurodegenerative dementia and making best use of any available therapies. This latter opportunity is unique and should not be lost.