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Wireless device developed to detect Alzheimer’s and Parkinson’s biomarkers

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Biosensor for Alzheimer's and Parkinson's biomarkers

An international team of researchers has developed a handheld, non-invasive device that can detect biomarkers for Alzheimer’s and Parkinson’s Diseases.

The team tested the device on in vitro samples from patients and showed that it is as accurate as current state-of-the-art methods. Ultimately, researchers plan to test saliva and urine samples with the biosensor.

The device, which transmits the results wirelessly to a laptop or smartphone, could be modified to detect biomarkers for other conditions as well.

The device relies on electrical rather than chemical detection, which researchers say is easier to implement and more accurate.

“This portable diagnostic system would allow testing at-home and at point of care, like clinics and nursing homes, for neurodegenerative diseases globally,” said Ratnesh Lal, a bioengineering, mechanical engineering and materials science professor at the UC San Diego Jacobs School of Engineering and one of the paper’s corresponding authors.

By the year 2060, about 14 million Americans will suffer from Alzheimer’s Disease.

Other neurodegenerative diseases, such as Parkinson’s, are also on the rise. Current state-of-the-art testing methods for Alzherimer’s and Parkinson’s require a spinal tap and imaging tests, including an MRI.

As a result, early detection of the disease is difficult, especially when many patients feel hesitant about invasive procedures. Testing is also difficult for patients who are already exhibiting symptoms and have difficulty moving, along with those who have no early access to local hospitals or medical facilities.

One of the prevailing hypotheses in the field, which Lal has focused on, is that Alzheimer’s Disease is caused by soluble amyloid peptides that come together in larger molecules, which in turn form ion channels in the brain.

Lal wanted to develop a test that could non-invasively detect amyloid beta and tau peptides – biomarkers for Alzheimer’s – and alpha synuclein proteins – a biomarker for Parkinson’s UK awards over £1.8m to fund research He also wanted to rely on electrical rather than chemical detection, as he believes it is easier to implement and more accurate.

Additionally, it was important to Lal that the device could wirelessly transmit the test results to the patient’s family and physicians.

“I am trying to improve quality of life and save lives,” he said.

To realise this vision, he and his colleagues adapted a device they developed during the COVID pandemic to detect the spike and nucleoprotein proteins in the live SARS-CoV-2 virus. That breakthrough had been made possible by chip miniaturisation and by large-scale automation of biosensor manufacturing.

The device consists of a chip with a high-sensitivity transistor, commonly known as a field effect transistor (FET). In this case, each transistor is made of a graphene layer that is a single atom thick, with three electrodes connected to the positive and negative poles of a battery and a gate electrode to control the amount of current flow.

Connected to the gate electrode is a single DNA strand, which serves as a probe that specifically binds to either amyloid beta, tau or synuclein proteins. The binding of these amyloids with their specific DNA strand probe changes the amount of current flow between the source and drain electrode. The change in this current or voltage is the signal used to detect specific biomarkers, like amyloids or COVID-19 proteins.

The research team tested the device with brain-derived amyloid proteins from Alzheimer’s and Parkinson’s deceased patients. The experiments showed that the biosensors could detect the specific biomarkers for both conditions with high accuracy, on par with existing methods. The device also works at extremely low concentrations, meaning that samples need only be a few microliters.

Tests showed that the device performed well even when the samples contained other proteins. Tau proteins were more difficult to detect, but because the device looks at three different biomarkers, it can combine results from all of these to arrive at a reliable overall result.

The technology has been licensed from UC San Diego to a biotechnology startup Ampera Life.

The next steps include testing blood plasma and cerebrospinal fluid with the device, then finally saliva and urine samples. The tests would take place in hospital settings and nursing homes. If these tests go well, Ampera Life plans to apply for FDA approval for the device, hopefully in the next five or six months. The ultimate goal is to bring the device to market in a year.

Funding for the research came from the National Institutes of Health, the University of California San Diego and the Chinese Academy of Sciences.

Researchers presented their findings in the 13 November 2023 issue of the Proceedings of the National Academy of Sciences. 

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How older people explore new spaces could suggest dementia

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Results from a new study have shown an analogous shift in exploration behaviour in middle age for the first time in humans.

Spatial navigation – the ability to select and follow a route from one place to another – is a skill we use every day. Depending on practice, general cognitive ability, and childhood environment, some people are naturally better at this than others.

However, research has also shown that people’s skill in spatial navigation tends to decrease with increasing age.

This decline in navigation skill has been generally attributed to worsening spatial memory, due to changes in brain structure and function that naturally occur with age. But what if it isn’t just due to our spatial memory declining, but also to changes in how we explore a novel environment? Such a shift has been observed in aging animals, ranging from insects to rodents and fish.

An exploratory study

Results from this new study, published in Frontiers in Aging Neuroscience, could have clinical applications.

First author Dr Vaisakh Puthusseryppady, a postdoctoral researcher at the University of California at Irvine, stated: “Compared to younger individuals, middle-aged people exhibit overall less exploration when learning a novel maze environment, and seem to be prioritising learning specific important locations in the maze as opposed to the overall maze layout.”

Puthusseryppady and colleagues recruited 87 middle-aged (on average 50 years old) and 50 young (on average 19 years old) women and men as volunteers. None had a history of neurologic disease including dementia, or psychiatric illness.

The researchers tested how well the volunteers explored and learned to navigate a maze in virtual reality. The maze was composed of crossroads and corridors, separated by hedges. Distinctive objects were scattered around it at strategic locations as landmarks. In the first ‘exploration phase’, the volunteers were instructed to freely explore the maze and learn the locations of the objects.

In each of the 24 trials in the second ‘wayfinding phase’, the volunteers had to apply what they had learnt, navigating between two randomly chosen objects within 45 seconds.

As expected, young people on average had a greater success rate in finding their way. But importantly, further statistical analyses showed that this difference in success rate was partially driven by observed qualitative changes in how young vs middle-aged participants learned about the maze.

“Compared to younger individuals, middle-aged individuals explored the maze environment less, as they travelled less distance, paused for longer periods of time at decision points, and visited more objects than young individuals,” said Dr Mary Hegarty, a professor at the Department of Psychological and Brain Sciences of the University of California at Santa Barbara, and a joint corresponding author.

These differences were so notable, the authors were able to predict using artificial intelligence whether a participant was middle-aged or young.

Pointing the way for applications

Reduced exploration in middle-aged people may be due to age-related changes in the brain’s navigation network, for example the medial temporal and parietal lobes.

The authors speculated that these findings could inform training interventions that can help middle-aged adults to improve their navigation abilities and preserve cognitive ability.

Co-author Daniela Cossio, a PhD student at the University of California at Irvine, explained: “If we were to train middle-aged people to explore novel environments better – with a focus on traveling greater distances, visiting paths that connect the environment, in a more spread-out manner – this might lead to improvements in their spatial memory, helping to slow down their decline in cognitive ability.”

Dr Elizabeth Chrastil, one of the corresponding authors, and an associate professor at the same institute, looked ahead: “We are currently investigating whether these kinds of changes in exploration behaviour can be identified in people at risk of Alzheimer’s Disease, as well as in those who actually have Alzheimer’s.

“We anticipate that altered exploration behaviour could ultimately become a novel clinical marker for early cognitive decline related to Alzheimer’s.”

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Lung cancer screening prolongs lives in real-world study

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Among US veterans diagnosed with lung cancer through the Veterans Health Administration healthcare system, those who underwent screening before diagnosis were more likely to be diagnosed with earlier stage disease and had a higher cure rate than those who had not been screened.

Lung cancer is the leading cause of cancer deaths worldwide, and most patients are diagnosed at an advanced stage.

Early detection through screening could save lives, and current recommendations state that adults 50–80 years old with at least a 20-pack-year smoking history who currently smoke or have quit within the past 15 years should undergo annual imaging tests for lung cancer.

Such screening has been shown to be beneficial in clinical trials, but there are limited data on the real-world effectiveness of lung cancer screening. To investigate, researchers assessed the impact of screening among patients in the Veterans Health Administration healthcare system diagnosed with lung cancer from 2011–2018.

Among 57,919 individuals diagnosed with lung cancer, 2,167 (3.9%) underwent screening before diagnosis. Patients who underwent screening had higher rates of early (stage I) diagnoses compared with those who had no screening (52% versus 27%), lower rates of death from any cause (49.8% versus 72.1%), and death from cancer (41.0% versus 70.3%) over 5 years.

“It is incredible to witness how dedicated national efforts to increase lung cancer screening from the Lung Precision Oncology Program can lead to substantial improvements in lung cancer outcomes,” said co–corresponding author Michael Green, MD, PhD, of the University of Michigan and the Veterans Affairs Ann Arbor Healthcare System.

The findings come from an observational study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

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Pioneering therapy approach to combat age-related vision loss

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Cirrus Therapeutics, the University of Bristol, and London’s Global University Institute of Ophthalmology have discovered a revolutionary treatment for age-related macular degeneration (AMD), the leading cause of vision loss among older adults.

Featured on the cover of the journal Science Translational Medicine, this breakthrough research reveals that boosting a specific protein, IRAK-M, in retinal cells could offer a new and highly effective therapy for AMD.

AMD can severely impact a person’s vision. Patients suffering from AMD often start with blurred vision or seeing a black dot in their central vision, which can ultimately expand to the point where there is no useful central vision. Currently, AMD affects approximately 200 million people worldwide, a number projected to rise to 288 million by 2040 with graying populations.

The exact cause of AMD is complex and thought to involve a combination of aging, environmental, and lifestyle factors.

The team found that augmenting IRAK-M levels in retinal cells can significantly protect against retinal degeneration.

“This discovery represents the first pathway-agnostic approach toward AMD, offering a comprehensive treatment option for the millions of people who suffer from this debilitating condition,” said Dr. Andrew Dick, Head of the Academic Unit of Ophthalmology at the University of Bristol, Director of the UCL Institute of Ophthalmology, and co-founder and Chief Scientific Advisor of Cirrus Therapeutics.

Dr. Jian Liu, the first author and senior research scientist at the Academic Unit of Ophthalmology of the University of Bristol, added: “Since age stands as a primary risk factor for AMD, the gradual decrease of IRAK- M levels with age, which further declines in AMD, is a key way to identify the potential markers of early AMD progression and ultimately a new way of treatment.”

This discovery will build and improve upon current treatments for AMD, which are targeting single pathophysiology pathways. “Our novel approach not only addresses the multiple pathways involved in treating AMD but also offers the most compelling and evidence-based strategy available today,” said Cirrus Therapeutics co-founder and Chief Executive Officer Dr. Ying Kai Chan.

Cirrus Therapeutics recently spun out of the University of Bristol to develop therapies related to this discovery.

The research for this paper was funded by the Rosetrees Trust, Stoneygate Trust, Underwood Trust, Macular Society, Sight Research UK, Moran Eye Center at the University of Utah, Sharon Eccles Steele Center for Translation, and supported by the National Institute for Health and Care Research (NIHR) BRC Moorfields and UCL-Institute of Ophthalmology.

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