Velandy Manohar, MD

Distinguished Life Fellow, Am. Psychiatric Association,

Past Steering Comm and Founding member of the Psychotherapy Caucus of the APA

Alzheimer's and COVID-19 share a genetic risk factor | MDLinx

[Annotated Review.VM]

Alzheimer's and COVID-19 share a genetic risk factor

MedicalXpress Breaking News-and-Events|October 8, 2021

An anti-viral gene that impacts the risk of both Alzheimer's disease and severe COVID-19 has been identified by a UCL-led research team.

The researchers estimate that one genetic variant of the OAS1 gene increases the risk of Alzheimer's disease by about 3-6% in the population as a whole, while related variants on the same gene increase the likelihood of severe COVID-19 outcomes.

The findings, published in Brain, could open the door for new targets for drug development or tracking disease progression in either disease, and suggest that treatments developed could be used for both conditions. The findings also have potential benefits for other related infectious conditions and dementias.

Lead author Dr. Dervis Salih (UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL) said: "While Alzheimer's is primarily characterized by harmful build-up of amyloid protein and tangles in the brain, there is also extensive inflammation in the brain that highlights the importance of the immune system in Alzheimer's. We have found that some of the same immune system changes can occur in both Alzheimer's disease and COVID-19.

"In patients with severe COVID-19 infection there can also be inflammatory changes in the brain. Here we have identified a gene that can contribute to an exaggerated immune response to increase risks of both Alzheimer's and COVID-19."

For the study the research team sought to build on their previous work, which found evidence from a large dataset of human genomes, to suggest a link between the OAS1 gene and Alzheimer's disease.

The OAS1gene is expressed in microglia, a type of immune cell that constitutes around 10% of all cells found within the brain. Investigating the gene's link to Alzheimer's further, they sequenced genetic data from 2,547 people, half of whom had Alzheimer's disease. They found that people with a particular variation, called rs1131454, of the OAS1 gene were more likely to have Alzheimer's disease, increasing carriers' baseline risk of Alzheimer's by an estimated 11-22%. The new variant identified is common, as just over half of Europeans are believed to carry it, and it has a bigger impact on Alzheimer's risk than several known risk genes.

Their findings add OAS1, an anti-viral gene, to a list of dozens of genes now known to affect a person's risk of developing Alzheimer's disease.

The researchers investigated four variants on the OAS1 gene, all of which dampen its expression (activity). They found that the variants increasing the risk of Alzheimer's disease are linked (inherited together) with OAS1variants recently found to increase the baseline risk of needing intensive care for COVID-19 by as much as 20%.

As part of the same research, in immune cells treated to mimic the effects of COVID-19, the researchers found that the gene controls how much the body's immune cells release pro-inflammatory proteins. They found that microglia cells where the gene was expressed more weakly had an exaggerated response to tissue damage, unleashing what they call a 'cytokine storm,' which leads to an autoimmune state where the body attacks itself.

OAS1activity changes with age, so further research into the genetic network could help to understand why older people are more vulnerable to Alzheimer's, COVID-19, and other related diseases.

 

In patients with severe COVID-19 infection there can also be inflammatory changes in the brain. Here we have identified a gene that can contribute to an exaggerated immune response to increase risks of both Alzheimer's and COVID-19."

For the study the research team sought to build on their previous work, which found evidence from a large dataset of human genomes, to suggest a link between the OAS1 gene and Alzheimer's disease.

The OAS1gene is expressed in Microglia, a type of immune cell that constitutes around 10% of all cells found within the brain. Investigating the gene's link to Alzheimer's further, they sequenced genetic data from 2,547 people, half of whom had Alzheimer's disease. They found that people with a particular variation, called rs1131454, of the OAS1 gene were more likely to have Alzheimer's disease, increasing carriers' baseline risk of Alzheimer's by an estimated 11-22%. The new variant identified is common, as just over half of Europeans are believed to carry it, and it has a bigger impact on Alzheimer's risk than several known risk genes.

Their findings add OAS1, an anti-viral gene, to a list of dozens of genes now known to affect a person's risk of developing Alzheimer's disease.

The researchers investigated four variants on the OAS1 gene, all of which dampen its expression (activity). They found that the variants increasing the risk of Alzheimer's disease are linked (inherited together) with OAS1variants recently found to increase the baseline risk of needing intensive care for COVID-19 by as much as 20%.

 

As part of the same research, in immune cells treated to mimic the effects of COVID-19, the researchers found that the gene controls how much the body's immune cells release pro-inflammatory proteins. They found that microglia cells where the gene was expressed more weakly had an exaggerated response to tissue damage, unleashing what they call a 'cytokine storm,' which leads to an autoimmune state where the body attacks itself.

OAS1activity changes with age, so further research into the genetic network could help to understand why older people are more vulnerable to Alzheimer's, COVID-19, and other related diseases.

Ph.D. student Naciye Magusali (UK Dementia Research Institute at UCL) said: "Our findings suggest that some people may have increased susceptibility to both Alzheimer's disease and severe COVID-19, irrespective of their age, as some of our immune cells appear to engage a common molecular mechanism in both diseases."

Following the outbreak of the COVID-19 pandemic, researchers from the UK Dementia Research Institute at UCL have pivoted their attention to investigating the long-term neurological consequences of the virus. Using biomarkers found in the blood and fluid surrounding the central nervous system, they are aiming to track neuroinflammation and injury to the neurons.

Dr. Salih said: "If we could develop a simple way of testing for these genetic variants when someone tests positive for COVID-19, then it might be possible to identify who is at greater risk of needing critical care, but there is plenty more work to be done to get us there. Similarly, we hope that our research could feed into the development of a blood test to identify whether someone is at risk of developing Alzheimer's before they show memory problems.

"We are also continuing to research what happens once this immune network has been activated in response to an infection like COVID-19, to see whether it leads to any lasting effects or vulnerabilities, or if understanding the brain's immune response to COVID-19, involving the OAS1gene, may help to explain some of the neurological effects of COVID-19."To read more, click here

 

I will be glad to provide more details [in the form of an annotated review of the information available on these two books, than is available in these posts about the interactions between Diet, Metabolic Syndrome, the Microbiome which influences the onset, course, variations in severity of Inflammatory processes that are elicited by Sustained stress/trauma and is at the core of many disorders including Major Depression, CHD, Stroke, caner, HIV. I have also outlined the influence of Positive Emotions and the leverage the Ventral  and Dorsal vagal systems can exert on immune system, and course of inflammation and MH and Medical Disorders. Also, please review related information on professional website velandymanoharmd.com

I.A.

5 Ways to Prevent Dementia, Says Dr. Sanjay Gupta (yahoo.com)

Dr. Sanjay Gupta, MD: Stay Sharp: Build a Better Brain at Any Age.5 Ways to Prevent Dementia, Says Dr. Sanjay Gupta. His 5 ways of preventing Dementia and the elements of the acronym PROOF that he recommends we can adopt to Pandemic proof ourselves ahead of the next Pandemic in his new book overlap and find harmony quite well to my acronym that addresses my key priorities for restoring our health and re-experiencing Wellbeing namely SENSS. [ I had clarifying moment when I was discussing my recommendations with a colleague, and I said – I have come to my senses and am healthier ow personally after adopting these recommendations for a few years and working with five physicians to address life threatening illnesses.

I. B.

Dr. Sanjay Gupta's new book offers tips on becoming 'pandemic-proof' (palmbeachpost.com)

CNN expert Gupta's new book offers pandemic lessons for today — and the future. "World War C: Lessons from the COVID-19 Pandemic and How to Prepare for the Next One."

II. A.

HealthPromotionEducationalMaterials

These are my recommendations Velandy Manohar, MD

II. B.

TreatmentRecommendationsforRestoringWellbeing.

 

These are my recommendations for recovering from Major Depressive Disorder.

There is great overlap between these concepts and what I have been teaching in the Health Promoting Education materials I have written[ Especially with respect to the central role of Inflammation, the pervasive effects of the Microbiome and the Vagus N.]and distributed to my patients and staff for over a decade. I am providing the documents I developed from about 2010 when I was working  with Family Centered Integrated Care Team in a FQHC- Community Health Center, Middletown, CT

II. C.

ARC Health Promotion Response to Food and Nutrition Service (psychiatristsites.com)

This is my response to the 2020 Dietary Guidelines Committee of the Food and Nutrition Services. I have provided a synopsis of my detailed documentation of my perspectives in II.A. and II.B.