A promising new approach to potentially treat Alzheimer’s disease – and also vaccinate against it – has been developed by a team of UK and German scientists.
Both the antibody-based treatment and the protein-based vaccine developed by the team reduced Alzheimer’s symptoms in mouse models of the disease. The research is published today in Molecular Psychiatry.
Rather than focus on the amyloid beta protein in plaques in the brain, which are commonly associated with Alzheimer’s disease, the antibody and vaccine both target a different soluble – form of the protein, that is thought to be highly toxic.
Amyloid beta protein naturally exists as highly flexible, string-like molecules in solution, which can join together to form fibres and plaques. In Alzheimer’s disease, a high proportion of these string-like molecules become shortened or ‘truncated’, and some scientists now think that these forms are key to the development and progression of the disease.
Professor Thomas Bayer, from the University Medical Center Göttingen, said: “In clinical trials, none of the potential treatments which dissolve amyloid plaques in the brain have shown much success in terms of reducing Alzheimer’s symptoms. Some have even shown negative side effects. So, we decided on a different approach. We identified an antibody in mice that would neutralise the truncated forms of soluble amyloid beta, but would not bind either to normal forms of the protein or to the plaques.”
Dr Preeti Bakrania and colleagues from LifeArc adapted this antibody so a human immune system wouldn’t recognise it as foreign and would accept it. When the Leicester research group looked at how and where this ‘humanised’ antibody, called TAP01_04, was binding to the truncated form of amyloid beta, the team had a surprise. They saw the amyloid beta protein was folded back on itself, in a hairpin-shaped structure.
Professor Mark Carr, from the Leicester Institute of Structural and Chemical Biology at the University of Leicester, explained: “This structure had never been seen before in amyloid beta. However, discovering such a definite structure allowed the team to engineer this region of the protein to stabilise the hairpin shape and bind to the antibody in the same way. Our idea was that this engineered form of amyloid beta could potentially be used as a vaccine, to trigger someone’s immune system to make TAP01_04 type antibodies.”
When the team tested the engineered amyloid beta protein in mice, they found that mice who received this ‘vaccine’ did produce TAP01 type antibodies.
The Göttingen group then tested both the ‘humanised’ antibody and the engineered amyloid beta vaccine, called TAPAS, in two different mouse models of Alzheimer’s disease. Based on similar imaging techniques to those used to diagnose Alzheimer’s in humans, they found that both the antibody and the vaccine helped to restore neuron function, increase glucose metabolism in the brain, restore memory loss and – even though they weren’t directly targeted – reduce amyloid beta plaque formation.
Release date: 16 November 2021
Source: University of Leicester
Coffee could lower risk of Alzheimer’s disease
Good news for those of us who can’t face the day without their morning flat white: a long-term study has revealed drinking higher amounts of coffee may make you less likely to develop Alzheimer’s disease.
As part of the Australian Imaging, Biomarkers and Lifestyle Study of ageing, researchers from Edith Cowan University (ECU) investigated whether coffee intake affected the rate of cognitive decline of more than 200 Australians over a decade.
Lead investigator Dr Samantha Gardener said results showed an association between coffee and several important markers related to Alzheimer’s disease.
‘Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study’ was published in Frontiers in Aging Neuroscience.
Release date: 23 November 2021
Source: Edith Cowan University
Plant-derived antiviral drug is effective in blocking highly infectious SARS-CoV-2 Delta variant
A plant-based antiviral treatment for Covid-19, recently discovered by scientists at the University of Nottingham, has been found to be just as effective at treating all variants of the virus SARS-CoV-2, even the highly infectious Delta variant.
The struggle to control the Covid-19 pandemic is made more difficult by the continual emergence of virulent SARS-CoV-2 variants, which are either more infectious, cause more severe infection, or both.
In a new study published in Virulence, a group of scientists, led by Professor Kin-Chow Chang from the School of Veterinary Medicine and Science at the University, found that the Delta variant, compared with other recent variants, showed the highest ability to multiply in cells, and was most able to directly spread to neighbouring cells. In co-infections with two different SARS-CoV-2 variants, the Delta variant also boosted the multiplication of its co-infected partners.
The study also showed that a novel natural antiviral drug called thapsigargin (TG), recently discovered by the same group of scientists to block other viruses, including the original SARS-CoV-2, was just as effective at treating all of the newer SARS-CoV-2 variants, including the Delta variant.
In their previous studies* the team showed that the plant-derived antiviral, at small doses, triggers a highly effective broad-spectrum host-centred antiviral innate immune response against three major types of human respiratory viruses, including SARS-CoV-2.
In this latest study, the team set out to find out how well the emergent Alpha, Beta and Delta variants of SARS-CoV-2 are able to multiply in cells relative to each other as single variant infections and in co-infections- where cells are infected with two variants at the same time. The team also wanted to know just how effective TG was at blocking these emergent variants.
Our new study has given us better insights into the dominance of the Delta variant. Even though we have shown that this variant is clearly the most infectious and promotes production of other variants in co-infections, we are pleased to have shown that TG is just as effective against all of them. Together, these results point to the antiviral potential of TG as a post-exposure prophylactic and an active therapeutic agent.” Professor Kin Chow Chang, lead author of the study
Release date: 19 November 2021
Source: University of Nottingham
Unborn babies could contract Covid-19 finds study, but it would be uncommon
An unborn baby could become infected with Covid-19 if their gut is exposed to the SARS-CoV-2 virus, finds a new study led by UCL researchers with Great Ormond Street Hospital for Children and the NIHR Great Ormond Street Biomedical Research Centre.
Although the study did not look specifically at mothers with Covid-19 and whether their infection was transmitted to an unborn baby, it found that certain fetal organs, such as the intestine, are more susceptible to infection than others.
However, researchers say, that opportunities for the Covid-19 virus infecting the fetus are extremely limited, as the placenta acts as a highly effective and protective shield, and evidence suggests fetal infection, known as vertical transmission, is extremely uncommon.
For the study, published in BJOG: An International Journal of Obstetrics & Gynaecology, researchers set out to understand how newborn babies could have developed Covid-19 antibodies, as has been reported in a small number of cases.
Specifically, they wanted to know if and how the virus could be passed from an infected mother to the unborn fetus.
To answer this question, researchers examined various fetal organs and placenta tissue to see if there was any presence of the cell surface protein receptors, ACE2 and TMPRSS2. These two receptors sit on the outside of cells and both are needed for the SARS-Cov-2 virus to infect and spread.
Researchers found the only fetal organs* to feature both the ACE2 and TMPRSS2 were the intestines (gut) and the kidney; however the fetal kidney is anatomically protected from exposure to the virus and is therefore less at risk of infection.
Therefore, the team concluded that the SARS-CoV-2 virus could only infect the fetus via the gut and through fetal swallowing of amniotic fluid, which the unborn baby does naturally for nutrients.
After birth ACE2 and TMPRSS2 receptors are known to be present in combination on the surface of cells in the human intestine as well as the lung. The gut and lung are suspected to be the main routes for Covid-19 infection, but in younger children, the intestine appears to be most important for virus infection.
Release date: 19 November 2021
Source: University College London
Optimized second-generation mRNA vaccine demonstrated improved protection against COVID-19 in preclinical testing
In a recent phase 2b/3 clinical trial, a third mRNA vaccine against COVID-19 — known as CVnCoV and developed by CureVac — reported approximately 48 percent efficacy against symptomatic disease. In a head-to-head test of a revised version of the vaccine, CV2CoV, researchers at Beth Israel Deaconess Medical Center (BIDMC) assessed the vaccines’ ability to provoke an immune response as well as their protective efficacy against COVID-19 in non-human primates. Their findings, published in Nature, show the modifications made to the second-generation CV2nCoV induced a ten-fold higher antibody response than the original version, CVnCoV.
Release date: 18 November 2021
Source: Deaconess Medical Center
Parental depression is associated with worse childhood mental health, educational attainment
Parental depression is a bigger risk factor if it occurs during a child’s lifetime.
Children who live with a parent who has depression are more likely to develop depression and to not achieve educational milestones, according to a new study published this week in the open-access journal PLOS ONE by Sinead Brophy of Swansea University, UK, and colleagues.
Maternal depression is a known risk factor for depression in children and is associated with a range of adverse child health and educational outcomes including poorer academic attainment. To date, however, risk factors associated with paternal depression have been less well examined. Understanding the effects of timing of both maternal and paternal depression of offspring outcomes has implications for prevention and early intervention.
Release date: 17 November 2021
Source: EurekAlert
Air Pollution Does Not Increase the Risk of Getting Infected but Does Increase the Risk of Getting Sick from COVID-19
A series of studies suggest that regions with higher pre-pandemic levels of air pollution had a higher incidence of COVID-19 cases and deaths. However, the reasons for this associations are not yet clear; air pollution could favor airborne transmission of the virus, or it could increase an individual’s susceptibility to infection or disease. “The problem is that previous studies were based on reported cases, which had been diagnosed, but missed all the asymptomatic or undiagnosed cases,” says Manolis Kogevinas, ISGlobal researcher and first author of the study.
The study included 9,605 participants among which there were 481 confirmed cases (5%). In addition, blood samples from over 4,000 participants were taken to determine the presence and quantity of IgM, IgA and IgG antibodies to five viral antigens. Of these, 18% had virus-specific antibodies, but no association was found between infection and exposure to air pollutants. However, among those who were seropositive (i.e. got infected), an association was found between higher exposure to NO2 and PM2.5 and higher levels of IgG specific for the five viral antigens (an indication of higher viral burden and/or symptom severity).
For the total study population (the 9,605 participants), an association was found between higher exposure to NO2 and PM2.5 and disease (symptoms), particularly for severe cases that ended in the hospital or in intensive care. The association with PM2.5 was stronger for men over 60 years of age and people living in socioeconomically deprived areas.
“Our study provides the strongest evidence globally on the association of ambient air pollution and COVID-19,” says Kogevinas. “These results are in line with the association between air pollution and hospitalization described for other respiratory diseases such as influenza or pneumonia”. Air pollution could also contribute by favouring the development of cardiovascular, respiratory or other chronic conditions, which in turn increase the risk of severe COVID-19.
Release date: 17 November 2021
Source: Barcelona Institute for Global Health (ISGlobal)
When older couples are close together, their heart rates synchronize
As couples grow old together, their interdependence heightens. Often, they become each other’s primary source of physical and emotional support. Long-term marriages have a profound impact on health and well-being, but benefits depend on relationship quality.
A new study from the University of Illinois examines the dynamics of long-term relationships through spatial proximity. The researchers find that when partners are close to each other, their heart rates synchronize in complex patterns of interaction.
But just being close to another person isn’t always beneficial; it depends on the nature of the interaction, Ogolsky points out. Closeness in the context of a conflict is very different from closeness in the context of a loving interaction. Similarly, changes in heart rate can be positive or negative.
Participants wore a Fitbit measuring their heart rate. They also wore a small proximity-sensing device. The researchers installed sensors in the home that allowed them to monitor the devices and observe in real time how physically close the spouses were to each other. They could then correlate all three measures – each partner’s heart rate and the couple’s proximity – in real time.
The researchers called the couples in the morning to remind them to put on the Fitbit and tracking device, and again in the evening for a survey about their health and well-being as well as their relationship dynamics throughout the day.
The paper, “Spatial proximity as a behavioral marker of relationship dynamics in older adult couples,” is published in the Journal of Social and Personal Relationships.
Release date: 16 November 2021
Source: University of Illinois
Regularly drinking tea and coffee associated with a lower risk of stroke and dementia
Researchers from China and the US found that people who drank two to three cups of tea and coffee a day had a lower risk of stroke and vascular dementia. Findings are published today (Tuesday 16 November) in the journal PLOS Medicine.
What did the scientists do?
This research involved volunteers from an existing large study, the UK Biobank, who were followed up over a period of 10-14 years. In total 365,682 participants, aged between 50 and 74, took part in the research.
Participants self-reported their tea and coffee drinking habits at the beginning of the study. Researchers then recorded the numbers of people who went on to have a stroke (2.8%) or develop Alzheimer’s disease or vascular dementia (1.4%).
What did the scientists find?
People who drank two to three cups of coffee with two to three cups of tea per day had around 30% lower risk of stroke and dementia when compared to those who didn’t consume either. This association was found for people who just drank either tea or coffee, as well as those who drank both.
People who had the lowest risk of developing dementia or stroke either:
Researchers in this study found that drinking tea and coffee was linked to a lower risk of having an ischaemic stroke (caused by a blocked blood vessel) and vascular dementia, rather than a haemorrhagic stroke (caused by a burst blood vessel) or Alzheimer’s disease.
Release date: 16 November 2021
Source: Alzheimer’ s Research
COVID Patients on SSRI Antidepressants Are Less Likely to Die
A large analysis of health records from 87 health care centers across the United States found that people taking a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), particularly fluoxetine, were significantly less likely to die of COVID-19 than a matched control group.
The results add to a body of evidence indicating that SSRIs may have beneficial effects against the worst symptoms of COVID-19, although large randomized clinical trials are needed to prove this.
The UCSF-Stanford research team analyzed electronic health records from the Cerner Real World COVID-19 de-identified database, which had information from almost 500,000 patients across the U.S. This included 83,584 adult patients diagnosed with COVID-19 between January and September 2020. Of those, 3,401 patients were prescribed SSRIs.
The large size of the dataset enabled researchers to compare the outcomes of patients with COVID-19 on SSRIs to a matched set of patients with COVID-19 who were not taking them, thus teasing out the effects of age, sex, race, ethnicity, and comorbidities associated with severe COVID-19, such as diabetes and heart disease, as well as the other medications the patients were taking.
The results showed that patients taking fluoxetine were 28 percent less likely to die; those taking either fluoxetine or another SSRI called fluvoxamine were 26 percent less likely to die; and the entire group of patients taking any kind of SSRI was 8 percent less likely to die than the matched patient controls.
Though the effects are smaller than those found in recent clinical trials of new antivirals developed by Pfizer and Merck, the researchers said more treatment options are still needed to help bring the pandemic to an end. JAMA Network Open
Release date: 15 November 2021
Source: University of California – San Francisco
New approach provides potential vaccine and treatment for Alzheimer’s
A promising new approach to potentially treat Alzheimer’s disease – and also vaccinate against it – has been developed by a team of UK and German scientists.
Both the antibody-based treatment and the protein-based vaccine developed by the team reduced Alzheimer’s symptoms in mouse models of the disease. The research is published today in Molecular Psychiatry.
Rather than focus on the amyloid beta protein in plaques in the brain, which are commonly associated with Alzheimer’s disease, the antibody and vaccine both target a different soluble – form of the protein, that is thought to be highly toxic.
Amyloid beta protein naturally exists as highly flexible, string-like molecules in solution, which can join together to form fibres and plaques. In Alzheimer’s disease, a high proportion of these string-like molecules become shortened or ‘truncated’, and some scientists now think that these forms are key to the development and progression of the disease.
Professor Thomas Bayer, from the University Medical Center Göttingen, said: “In clinical trials, none of the potential treatments which dissolve amyloid plaques in the brain have shown much success in terms of reducing Alzheimer’s symptoms. Some have even shown negative side effects. So, we decided on a different approach. We identified an antibody in mice that would neutralise the truncated forms of soluble amyloid beta, but would not bind either to normal forms of the protein or to the plaques.”
Dr Preeti Bakrania and colleagues from LifeArc adapted this antibody so a human immune system wouldn’t recognise it as foreign and would accept it. When the Leicester research group looked at how and where this ‘humanised’ antibody, called TAP01_04, was binding to the truncated form of amyloid beta, the team had a surprise. They saw the amyloid beta protein was folded back on itself, in a hairpin-shaped structure.
Professor Mark Carr, from the Leicester Institute of Structural and Chemical Biology at the University of Leicester, explained: “This structure had never been seen before in amyloid beta. However, discovering such a definite structure allowed the team to engineer this region of the protein to stabilise the hairpin shape and bind to the antibody in the same way. Our idea was that this engineered form of amyloid beta could potentially be used as a vaccine, to trigger someone’s immune system to make TAP01_04 type antibodies.”
When the team tested the engineered amyloid beta protein in mice, they found that mice who received this ‘vaccine’ did produce TAP01 type antibodies.
The Göttingen group then tested both the ‘humanised’ antibody and the engineered amyloid beta vaccine, called TAPAS, in two different mouse models of Alzheimer’s disease. Based on similar imaging techniques to those used to diagnose Alzheimer’s in humans, they found that both the antibody and the vaccine helped to restore neuron function, increase glucose metabolism in the brain, restore memory loss and – even though they weren’t directly targeted – reduce amyloid beta plaque formation.
Release date: 16 November 2021
Source: University of Leicester