The discovery of a new role for the brain’s immune cells could have implications for conditions including Alzheimer’s disease and stroke.
A research team has uncovered a vital but previously unknown role for microglia, immune cells that protect the brain from disease and injury, and help to regulate blood flow and maintain the brain’s critical blood vessels.
The researchers, from the University of Virginia School of Medicine, believe the findings could prove important in cognitive decline, dementia and stroke, among other conditions linked to diseases of the brain’s small vessels.
“Precise blood vessel function is critical to accommodate the extreme energy demands of the brain for normal brain function,” said UVA’s Ukpong B. Eyo, of UVA’s Department of Neuroscience, the UVA Brain Institute and UVA’s Center for Brain Immunology and Glia (BIG).
“These findings suggest previously unknown roles for these brain cells in the proper maintenance of blood delivery to the brain and provide novel opportunities to intervene in contexts where blood perfusion to the brain is impaired.”
The researchers believe their new findings could have significant implications for diseases that affect the small vessels of the brain. These conditions are thought to contribute to stroke, Alzheimer’s, loss of balance and mental decline, among other serious health problems.
“We are currently expanding this research into an Alzheimer’s disease context in rodents to investigate whether the novel phenomenon is altered in mouse models of the disease and determine whether we could target the mechanisms we uncovered to improve known deficits in blood flow in such a mouse model of Alzheimer’s,” Eyo said.
“Our hope is that these findings in the lab could translate into new therapies in the clinic that would improve outcomes for patients.”
Scientists have known that microglia play many important roles in the brain and that microglia also facilitate the formation of the brain’s complex network of blood vessels during development. In Alzheimer’s disease, for example, recent work suggests that the loss of the immune cells is thought to increase harmful plaque buildup in the brain.
Scientists have been unsure, however, what role microglia play in maintaining blood vessels in a normal, healthy brain. The new research reveals for the first time that the cells are critical support staff, tending the vessels and even regulating blood flow.
The UVA researchers identified microglia associating with the brain’s capillaries, determined what the immune cells do there and revealed what controls those interactions. Among the cells’ important responsibilities is helping to regulate the diameter of the capillaries and possibly restricting or increasing blood flow as needed.
“Researchers have been studying these cells in the living brain for over two decades but this is the first time we are able to get an idea of these mechanisms of microglia-blood vessel interaction,” said Eyo, an expert on microglia.
“It’s an exciting time to be the first to make these findings here at UVA.”
Support at your fingertips – new resources for family dementia carers
Dementia Carers Count (DCC) is a national charity offering free, life-changing, practical support for families living with dementia.
The charity has just launched its new Virtual Carers Centre and runs regular online learning sessions, enabling carers to access essential support wherever they are.
DCC gives family carers the opportunity to understand more about dementia, to connect with others in a similar situation and to look after themselves while navigating the highs and lows of caring for someone with dementia.
It’s the ideal place to signpost carers to, for information and resources to help them with their day to day challenges.
Here is Stuart’s story.
Stuart met Roger in 1985, they’ve been in a registered partnership since 1995. Roger was diagnosed with young-onset Alzheimer’s when he was 57.
Roger has deteriorated considerably since his diagnosis and, as well as caring for him full time, Stuart has had to take on more and more at home.
Although Roger’s interests have changed his mood has remained good. He’s always smiling, and people tend to be drawn to him.
Stuart feels a bit frustrated now that he’s increasingly having to do more and more for Roger. He didn’t choose to be a carer and thought that by now, he would be enjoying my retirement and living happily ever after.
At the start of the pandemic Stuart began using technology like Zoom. He first found out about Dementia Carers Count (DCC) in an online, young-onset support group. He registered for some of DCC’s online learning sessions.
“The online courses have been like gold dust and have increased my knowledge of dementia and Alzheimer’s. The people leading the sessions are easy-going, supportive and understanding…. They’ve been a lifeline for people like me during the pandemic.”
“DCC’s digital services are fantastic. They are very informative, accessible, and the content is presented in a way that is easy to understand. During the sessions, you can talk about your specific challenges and connect with the other people attending. “
Stuart says that the support DCC provides him has helped him immensely and is extremely useful to anyone in a caring situation.
“The information comes from people with experience and knowledge. It will help you understand what is going on for the person you care for and develop a better caring strategy. Everyone running the sessions is very patient and nurturing towards the people attending.”
DCC is here to help families living with dementia.
DCC’s Virtual Carers Centre is a brand new resource for family or friends who are looking after someone with dementia. It’s accessible any time; day or night, complete with articles, videos, presentations and more.
Carers will find all the support they need, including:
✔️ Practical information about carers’ rights and benefits
✔️How to manage everyday emotions and changes in behaviour
✔️Wellbeing strategies for carers and for the person they are supporting
✔️The opportunity to book on to Live Online Learning sessions covering various topics
T: 020 3096 7895 E: email@example.com
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De-cluttering ‘may not help’ with dementia
People with moderate dementia performed better when surrounded by their usual clutter, a new study has revealed
A clutter-free environment may not help people with dementia carry out daily tasks in the way that has traditionally been thought, a new study has revealed.
Researchers at the University of East Anglia (UEA) studied whether people with dementia were better able to carry out tasks, such as making a cup of tea, at home – surrounded by their usual clutter – or in a clutter-free environment.
And they admit to being “surprised” to find that participants with moderate dementia performed better when surrounded by their usual clutter.
But the different environments made no difference to people with mild and severe dementia, who were able to perform at the same level in both settings.
Professor Eneida Mioshi, from UEA’s School of Health Sciences, said: “The majority of people with dementia live in their own home and usually want to remain living at home for as long as possible.
“So it’s really important to know how people with dementia can be best supported at home – one possible route would be by adapting the physical environment to best suit their needs.
“As dementia progresses, people gradually lose their ability to carry out daily tasks due to changes in their cognitive, perceptual and physical abilities. Participation in daily tasks could then be improved by adapting the person’s environment.
“To this end, we wanted to investigate the role of clutter in activity participation, given the potential to use de-cluttering to support people with dementia to continue to be independent.
“Environmental clutter has been defined as the presence of an excessive number of objects on a surface or the presence of items that are not required for a task.
“It is generally assumed that a person with dementia will be better able to carry out daily tasks when their home space is tidy and clutter free.
“However, there has been very little research to really test this hypothesis.
“We wanted to see whether clutter was negatively affecting people with dementia. So we studied how people at different stages of dementia coped with carrying out daily tasks at home, surrounded by their usual clutter, compared to in a clutter-free setting – a specially designed home research lab.”
Occupational therapist and PhD student Julieta Camino carried out the study with 65 participants who were grouped into those with mild, moderate and severe dementia.
They were asked to carry out daily tasks including making a cup of tea and making a simple meal, both at their own home and at UEA’s specially-designed NEAT research bungalow – a fully furnished research facility that feels just like a domestic bungalow.
The researchers evaluated performance of activities in both settings, and also measured the amount of clutter in the participants’ homes. Meanwhile, the NEAT home setting was completely clutter free.
Julieta, also from UEA’s School of Health Sciences, said: “We thought that the complete absence of clutter in our research bungalow would play a beneficial role in helping people with dementia with daily living activities. But we were wrong.
“We were surprised to find that overall, people with moderate dementia, in particular, performed daily tasks better at home – even though their homes were significantly more cluttered than our research bungalow.
“And it didn’t seem to make any difference how cluttered the participant’s home was. The only factor that contributed to how well they could carry out tasks at home was their level of cognition – with those with severe dementia encountering the same difficulties to perform the tasks at home and in the research bungalow.”
This research received funding from the Alzheimer’s Society and National Institute of Health Research (NIHR) Applied Research Collaboration East of England (ARC EoE) programme.
New drug design could yield Alzheimer’s treatments
The breakthrough could have the potential to create superior new drugs to improve cognitive function in Alzheimer’s disease patients
A breakthrough ‘bench to bedside’ discovery, ten years in the making, has been made in the quest to advance the future treatment of Alzheimer’s disease in patients.
The research illustrates – for the first time – the process of designing a new molecule to selectively target a specific receptor protein in the brain and demonstrating, through laboratory preclinical and human clinical studies.
The breakthrough has been hailed as having the potential to create superior new drugs to improve cognitive function in Alzheimer’s Disease patients.
The study – conducted at the University of Glasgow with Sosei-Heptares Ltd – was focused on new molecules, designed by the biotechnology company, that selectively target a protein called the M1 muscarinic acetylcholine receptor (or M1 receptor, a G protein-coupled receptor or GPCR) in the brain, which is known to play a central role in memory and cognition.
Subsequent translational medicine studies tested the hypothesis that such molecules will retain cognitive benefits and lack dose-limiting side effects.
The international research team demonstrated that an exquisitely selective modulator could be successfully designed using detailed knowledge of the M1 receptor’s 3D structure, despite its very close similarity to other types of muscarinic receptor. This approach is known as structure-based drug design or SBDD.
Subsequent pre-clinical studies confirmed the designed molecule retained optimal properties for improving memory while minimising side effects associated with previous attempts to target the M1 receptor.
Finally, clinical studies demonstrated that the M1-selective clinical candidate HTL9936, at meaningful doses in healthy volunteers, showed greatly reduced side effects relative to many non-selective predecessors from programmes spanning a generation of traditional drug discovery approaches.
These ground-breaking results substantiate the hypothesis and the power of novel approaches using 3D structures of receptors developed by the team can be applied to the M1 receptor to create a potential new medicine for Alzheimer’s Disease patients, and also have broader implications highlighting a new approach to address other GPCRs linked to a wide range of diseases.
Prof. Andrew Tobin, professor of molecular pharmacology and director of the newly-built Advanced Research Centre at the University of Glasgow, said: “This is a true bench-to-bedside discovery, many years in the making, and we are thrilled that this hugely important and global collaboration with our partners at Sosei Heptares and others has resulted in a highly sophisticated drug design approach that offers huge potential to improve the treatment of Alzheimer’s Disease, by activating memory and cognitive centres within the brain.
“We are extremely encouraged by our findings so far and are very hopeful that this could lead to new treatment options for patients with this devastating disease.”
Dr Miles Congreve, chief scientific officer at Sosei Heptares, added: “We are delighted that this pioneering drug design work in collaboration with Prof. Tobin and others has been published in such a highly acclaimed journal.
“The precision SBDD technology that we have developed is core to our approach at Sosei Heptares and has been extremely effective for designing new and superior drug molecules that we are progressing through preclinical and clinical development as potential new treatments for a wide range of neurological, immunological and gastrointestinal diseases.”
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