Scientists are investigating a small region of the brain that plays a major role in memory, spatial navigation, and perhaps Alzheimer’s disease. One of the first parts of the brain affected by Alzheimer’s disease is the entorhinal cortex – a region that plays a big role in memory, spatial navigation, and the brain’s internal mapping system.
With support announced in September from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, Virginia Tech scientists Sharon Swanger and Shannon Farris are working to understand why this area is especially vulnerable.
Swanger studies how brain cells communicate across synapses, while Farris focuses on how memory at the molecular level. Their overlapping expertise made the collaboration a natural fit.
“We’ve both been studying for a while,” said Swanger, assistant professor at the Fralin Biomedical Research Institute at VTC. “This new collaborative project brings together my work on synapses and Shannon’s on mitochondria in a way that addresses a big gap in the field.”
“This kind of state-level support is critical,” said Farris, also an assistant professor at the research institute. “It gives researchers in Virginia the chance to ask questions that may eventually make a difference for people living with Alzheimer’s. It’s meaningful to be part of research that could help people facing that journey.”
A key focus of their research is mitochondria – tiny structures inside brain cells that provide the energy needed for a variety of cellular functions in neurons including transmission. In Alzheimer’s disease, mitochondria stop working properly early in the course of the disease.
Farris and Swanger are investigating whether mitochondria in a vulnerable memory-related circuit may become overloaded with calcium, a key signaling chemical for multiple neuronal and synaptic processes. That overload could contribute to the early breakdown of memory.
“The connection between these cells is one of the first to fail in Alzheimer’s,” Farris said. “We found that this synapse has unusually strong calcium signals in nearby mitochondria – so strong we can see them clearly under a light microscope. Those kinds of signals are hard to ignore. It gives us a model where we can really watch what’s happening as things start to go wrong.”
To test their hypothesis, the researchers will study brain tissue from healthy mice and mice with Alzheimer’s. By comparing how mitochondria function and how brain cells communicate across synapses in each group, they hope to find early signs of stress or failure in the entorhinal cortex–hippocampus circuit.
Researchers from the Broad Institute and Mass General Brigham have shown that a low-oxygen environment – similar to the thin air found at Mount Everest base camp – can protect the brain and restore movement in mice with Parkinson’s-like disease.
The new research, in Nature Neuroscience, suggests that cellular dysfunction in Parkinson’s leads to the accumulation of excess oxygen molecules in the brain, which then fuel neurodegeneration – and that reducing oxygen intake could help prevent or even reverse Parkinson’s symptoms.
“The fact that we actually saw some reversal of neurological damage is really exciting,” said co-senior author Vamsi Mootha, an institute member at the Broad, professor of systems biology and medicine at Harvard Medical School, a Howard Hughes Medical Institute investigator in the Department of Molecular Biology at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “It tells us that there is a window during which some neurons are dysfunctional but not yet dead – and that we can restore their function if we intervene early enough.”
“The results raise the possibility of an entirely new paradigm for addressing Parkinson’s disease,” added co-senior author Fumito Ichinose, the William T. G. Morton professor of anesthesia at Harvard Medical School and MGH.
The researchers caution that it’s too soon to translate these results directly to new treatments for patients. They emphasize that unsupervised breathing of low-oxygen air, especially intermittently such as only at night, can be dangerous and may even worsen the disease. But they’re optimistic their findings could help spur the development of new drugs that mimic the effects of low oxygen.
The study builds on a decade of research from Mootha and others into hypoxia – the condition of having lower than normal oxygen levels in the body or tissues – and its unexpected ability to protect against mitochondrial disorders.
“We first saw that low oxygen could alleviate brain-related symptoms in some rare diseases where mitochondria are affected, such as Leigh syndrome and Friedreich’s ataxia,” said Mootha, who leads the Friedreich’s Ataxia Accelerator at Broad. “That raised the question: Could the same be true in more common neurodegenerative diseases like Parkinson’s?”
Eizo Marutani, an instructor of anesthesia at MGH and Harvard Medical School, is the first author of the new paper.
A long-standing link
Parkinson’s disease, which affects more than 10 million people worldwide, causes the progressive loss of neurons in the brain, leading to tremors and slowed movements. Neurons affected by Parkinson’s also gradually accumulate toxic protein clumps called Lewy bodies. Some biochemical evidence has suggested that these clumps interfere with the function of mitochondria, that Mootha knew were altered in other diseases that could be treated with hypoxia.
Moreover, anecdotally, people with Parkinson’s seem to fare better at high altitudes. And long-term smokers – who have elevated levels of carbon monoxide, leading to less oxygen in tissues – also appear to have a lower risk of developing Parkinson’s.
“Based on this evidence, we became very interested in the effect of hypoxia on Parkinson’s disease,” said Ichinose.
Mootha and Ichinose turned to a well-established mouse model of Parkinson’s in which animals are injected with clumps of the α-synuclein proteins that seed the formation of Lewy bodies. The mice were then split into two groups: one breathing normal air (21% oxygen) and the other continuously housed in chambers with 11% oxygen – comparable to living at an altitude of about 4800m.
A new paradigm for Parkinson’s
The results were striking. Three months after receiving α-synuclein protein injections, the mice breathing normal air had high levels of Lewy bodies, dead neurons, and severe movement problems. Mice that had breathed low-oxygen air from the start didn’t lose any neurons and showed no signs of movement problems, despite developing abundant Lewy bodies.
The findings show that hypoxia wasn’t stopping the formation of Lewy bodies but was protecting neurons from the damaging effects of these protein clumps – potentially suggesting a new mode of treating Parkinson’s without targeting α-synuclein or Lewy bodies, Ichinose said.
What’s more, when hypoxia was introduced six weeks after the injection, when symptoms were already appearing, it still worked. The mice’s motor skills rebounded, their anxiety-like behaviors faded, and the loss of neurons in the brain stopped.
To further explore the underlying mechanism, the team analyzed brain cells of the mice and discovered that mice with Parkinson’s symptoms had much higher levels of oxygen in some parts of the brain than control mice and those that had breathed low-oxygen air. This excess oxygen, the researchers said, likely results from mitochondrial dysfunction. Damaged mitochondria can’t use oxygen efficiently, so it builds up to damaging levels.
“Too much oxygen in the brain turns out to be toxic,” said Mootha. “By reducing the overall oxygen supply, we’re cutting off the fuel for that damage.”
Hypoxia in a pill
More work is needed before the findings can be directly used to treat Parkinson’s. In the meantime, Mootha and his team are developing “hypoxia in a pill” drugs that mimic the effects of low oxygen to potentially treat mitochondrial disorders, and they think a similar approach might work for some forms of neurodegeneration.
While not all neurodegenerative models respond to hypoxia, the approach has now shown success in mouse models of Parkinson’s, Leigh syndrome, Friedreich’s ataxia, and accelerated aging.
“It may not be a treatment for all types of neurodegeneration,” said Mootha, “but it’s a powerful concept – one that might shift how we think about treating some of these diseases.”
Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH
A recent study led by a team of researchers at The Johns Hopkins University School of Medicine examining aging mice has provided what is believed to be the first evidence that particles of amyloid beta protein, found in people with Alzheimer’s disease (AD), build up in the bone marrow of the animals, although not in the exact same form as the large, dense plaques found in the brains of people with Alzheimer’s disease.
“Although amyloid buildup has been found in organs outside the brain – such as the heart, kidneys, and nerves – it remains unclear whether similar deposits form in bone or bone marrow with aging or in Alzheimer’s disease,” says contributing study author Mei Wan, PhD, professor of the department of Orthopaedic Surgery. While brain amyloid has been extensively studied for its role in memory loss and neurodegeneration, far less is known about amyloid elsewhere in the body. In fact, almost nothing is known about whether amyloid forms in the skeleton or how it might contribute to age-related bone loss.”
AD is primarily associated with excessive amyloid plaques in the brain. Osteoporosis is a bone disease marked by low bone mineral density with an increased risk of fractures. Recent research suggests these two age-related conditions may be connected, and scientists are beginning to uncover common underlying causes.
Funded by the National Institutes of Health, the study findings, published in Nature Aging, advance scientific understanding of long-suspected similar biological processes that may be at work in osteoporosis – a form of bone loss – and Alzheimer’s dementia, the researchers say. The work may also offer potential new targets for preventing or treating bone loss.
The buildup of amyloid is triggered by fat cells in the bone marrow, known as bone marrow adipocytes (BMAds), and a protein they release called SAP/PTX2 in aged mice and mice with AD. These amyloid deposits impair bone-building cells (osteoblasts) and activate bone-resorbing cells (osteoclasts), leading to bone loss. In previous mouse models, removing senescent BMAds or blocking SAP/PTX2 have shown to significantly reduce amyloid buildup and restored bone health.
In this study, male and female mice ranging from 4 to 24 months were kept in a temperature-controlled room provided with ongoing access to food and water and exposed to a 12-hour light-dark cycle. Researchers put a concentration of 5mg/ml in the drinking water of the mice aged 18 months and examined the effects CPHPC had on their age-related bone loss. CPHPC (also named Miridesap) is a small molecule compound originally designed to treat amyloidosis which is a rare disease marked by the buildup of amyloid proteins. A control group of mice aged 4, 9, 22 and 24 months were given the same dosage of water without the CPHPC drug
High-resolution imaging of thigh and shin bones revealed amyloid fibrils forming ring-like structures around BMAds in aged mice and mice genetically engineered to have a form of AD. SAP/PTX2-driven amyloid clumps were found to enhance bone loss.
Study results also showed that CPHPC successfully depleted SAP/PTX2 and reversed bone deterioration in the older mice, suggesting a promising new therapeutic strategy for osteoporosis in the elderly, a strategy that would seek to eliminate aging fat cells or amyloid-promoting proteins.
Wan adds, “Our study is what we believe to be the first to show that harmful amyloid fibres (Aβ fibrils) build up in the bone marrow of aged mice. We also found that fat cells in the bone marrow release a protein called SAP/PTX2, which plays a major role in triggering this amyloid buildup and damaging bone. These findings uncover a new connection between bone loss and dementia risk and may open the door to new research on how protecting bone health could also help protect brain function.”
This discovery provides an opportunity for new treatments targeting bone aging and Alzheimer’s-associated osteoporosis by focusing on the elimination of senescent fat cells or amyloid-promoting proteins.
Analysis of lipid blood levels in women with Alzheimer’s disease has shown noticeable loss of unsaturated fats, such as those that contain omega fatty acids, compared to healthy women.
In men with Alzheimer’s, no significant difference was found in the same lipid molecule composition disease compared to healthy men, which suggests that those lipids have a different role in the disease according to sex. Fats perform important roles in maintaining a healthy brain, so this study could indicate why more women are diagnosed with the disease.
The study, published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association by scientists from King’s College London and Queen Mary University London, is the first to reveal the important role lipids could have in the risk for Alzheimer’s between the sexes.
Women are disproportionately impacted by Alzheimer’s Disease and are more often diagnosed with the disease than men after the age of 80. One of the most surprising things we saw when looking at the different sexes was that there was no difference in these lipids in healthy and cognitively impaired men, but for women this picture was completely different. The study reveals that Alzheimer’s lipid biology is different between the sexes, opening new avenues for research.
Dr Cristina Legido-Quigley, Reader in Systems Medicine
The scientists took plasma samples from 841 participants who had Alzheimer’s Disease, mild cognitive impairment and cognitively health controls and and were measured for brain inflammation and damage.
They used mass spectrometry to analyse the 700 individual lipids in the blood. Lipids are a group of many molecules. Saturated lipids are generally considered as ‘unhealthy’ or ‘bad’ lipids, while unsaturated lipid, which sometime contains omega fatty acids, are generally considered ‘healthy’.
Scientists saw a steep increase in lipids with saturation – the ‘unhealthy lipids’ – in women with Alzheimer’s compared to the healthy group. The lipids with attached omega fatty acids were the most decreased in the Alzheimer’s group.
Now, the scientists say there is a statistical indication that there is a causal link between Alzheimer’s Disease and fatty acids. But a clinical trial is necessary to confirm the link.
Dr Legido-Quigley added: “Our study suggests that women should make sure they are getting omega fatty acids in their diet – through fatty fish or via supplements. However, we need clinical trials to determine if shifting the lipid composition can influence the biological trajectory of Alzheimer’s Disease.”
Dr Asger Wretlind, first author of the study from the School of Cancer & Pharmaceutical Sciences, said: “Scientists have known for some time that more women than men are diagnosed with Alzheimer’s disease.
Although this still warrants further research, we were able to detect biological differences in lipids between the sexes in a large cohort, and show the importance of lipids containing omegas in the blood, which has not been done before. The results are very striking and now we are looking at how early in life this change occurs in women.
Dr Asger Wretlind, School of Cancer & Pharmaceutical Sciences
New research in Diabetes, Obesity and Metabolism reveals that metformin, a medication traditionally prescribed to treat diabetes, is linked to lower risks of dementia and early death.
In the study by investigators at Taipei Medical University that included 452,777 adults with varying degrees of overweight and obesity, 35,784 cases of dementia and 76,048 deaths occurred over 10 years. Metformin users exhibited significantly lower risks of both dementia and all-cause death than nonusers.
The benefits of metformin were seen across all categories of overweight, obesity, and severe obesity, with 8–12% lower risks of dementia and 26–28% lower risks of death.
“Although our study results are promising for metformin’s effects on dementia and mortality, further research is required to explore the mechanisms involved,” said co-corresponding author Chiehfeng Chen, MD, PhD, MPH.
People with Parkinson’s disease (PD) have an odour that can be reliably detected from skin swabs by trained dogs, a new study shows. The research, in collaboration with Medical Detection Dogs and the Universities of Bristol and Manchester, is published in The Journal of Parkinson’s Disease.
Two dogs were trained by the charity, Medical Detection Dogs, to distinguish between sebum swabs from people with and without Parkinson’s disease.
In a double blind trial, they showed sensitivity of up to 80% and specificity of up to 98%.
Not only that, they detected it in samples from patients who also had other health conditions.
The dogs were trained over a number of weeks on over 200 odour samples from individuals that had tested positive for PD and control samples from people who did not have the disease. Samples were presented to the dogs on a stand system and the dogs were rewarded for correctly indicating a positive sample and for correctly ignoring a negative sample.
In the double-blind testing, meaning that only a computer knew where the correct samples were, each line was also presented in reverse order so that samples for which no decision was made were re-presented. Then any unsearched samples were collected together in new lines, until a decision had been made for all samples.
A definitive diagnostic test for Parkinson’s Disease (PD) remains elusive, so identification of potential biomarkers could help diagnosis and timely intervention.
Claire Guest, Medical Detection Dogs CEO and Chief Scientific Officer, says: “We are extremely proud to say that once again, dogs can very accurately detect disease.
“There is currently no early test for Parkinson’s disease and symptoms may start up to 20 years before they become visible and persistent leading to a confirmed diagnosis.
“Timely diagnosis is key as subsequent treatment could slow down the progression of the disease and reduce the intensity of symptoms.”
Nicola Rooney, Associate Professor at Bristol Veterinary School at the University of Bristol and lead author, says: “Identifying diagnostic biomarkers of PD, particularly those that may predict development or help diagnose disease earlier is the subject of much ongoing research. The dogs in this study achieved high sensitivity and specificity and showed there is an olfactory signature distinct to patients with the disease. Sensitivity levels of 70% and 80% are well above chance and I believe that dogs could help us to develop a quick non-invasive and cost-effective method to identify patients with Parkinson’s disease.”
Perdita Barran, Professor of Mass Spectrometry at The University of Manchester, said: “It’s wonderful to be part of this research inspired by Joy Milne and our Nose2Diagnose programme. This study adds to the growing body of evidence showing that simple, non-invasive skin swabs can be used to diagnose Parkinson’s disease, offering a faster and more accessible method for early detection.”
The two dogs in the study were Golden Retriever, Bumper and Black Labrador, Peanut.
In the largest clinical trial to date, pramipexole was found to be substantially more effective than a placebo at reducing the symptoms of treatment resistant depression (TRD) over the course of nearly a year, when added to ongoing antidepressant medication.
The trial, supported by National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry,included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo, alongside ongoing antidepressant medication.
Overall, the group taking pramipexole experienced a significant and substantial reduction in symptoms by week twelve of treatment, with the benefits persisting over the course of a year. However, there were also significant side effects, such as nausea, sleep disturbance and dizziness, with around one in five people on pramipexole dropping out of the trial as a result.
Professor Michael Browning, from the Department of Psychiatry, University of Oxford, and workstream lead in Mood Disorders for the NIHR Mental Health-Translational Research Collaboration (MH-TRC) Mission, who led the trial, said: ‘Effectively treating people who have not responded to first-line interventions for depression is a pressing clinical problem and there has long been an urgent need to find new treatments.
‘These findings on pramipexole are a significant breakthrough for patients for whom antidepressants and other treatments and therapies have not worked.
‘Pramipexole is a medicine licensed for Parkinson’s disease and works by boosting the brain chemical dopamine. This differs from the majority of other antidepressant medications which act on brain serotonin and may explain why pramipexole was so helpful in this study.
‘We now need more research focusing on reducing the side effects of pramipexole, evaluating its cost-effectiveness, and comparing it with other add-on treatments.’
Previous research into using the drug for depression had shown promise, but there had been limited data on its long-term outcomes and side effects until now.
Current guidelines for people with treatment resistant depression recommend adding new treatments, such as lithium or antipsychotics, to ongoing antidepressant treatment, but these have limited effectiveness and do not work for everyone.
Phil Harvey, 72, from Oxfordshire, was diagnosed with depression 20 years ago and tried different tablets and counselling but nothing worked. Eventually he had to take a year off work before retiring. He started on the trial in 2022.
He said: ‘Within a few weeks I felt the effects, it was amazing. I kept a diary which they gave us on how my mood was, motivation and how it improved. It was dragging me out of this dark black hole that I’ve been in for years.’
Participants were recruited from across the country, including as part of the NIHR-funded MH-TRC Mission mood disorder clinics, which are hosted at Oxford but located across the country. The clinics efficiently, and largely remotely, assess patients with difficult to treat mood disorders and offer them enrolment in research studies. The network can also support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatment.
A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson’s disease, potentially replacing the need for multiple daily tablets.
UniSA PhD candidate Deepa Nakmode and Professor Sanjay Garg in the lab. Credit: UniSA
Scientists from the University of South Australia (UniSA) have developed a long-acting injectable formulation that delivers a steady dose of levodopa and carbidopa – two key medications for Parkinson’s – over an entire week.
The biodegradable formulation is delivered in a subcutaneous or intramuscular injection, where it gradually releases the medication over seven days.
Parkinson’s disease is the second most common neurological disorder, affecting more than 8.5 million people worldwide. Currently there is no cure and the symptoms – tremors, rigidity and slow movement – are managed with oral medications that must be taken several times a day.
The frequent dosing is a burden, especially for elderly patients or those with swallowing difficulties, leading to inconsistent medication levels, more side effects, and reduced effectiveness.
Lead researcher Professor Sanjay Garg, from UniSA’s Centre for Pharmaceutical Innovation, says the newly developed injectable could significantly improve treatment outcomes and patient adherence.
“Our goal was to create a formulation that simplifies treatment, improves patient compliance, and maintains consistent therapeutic levels of medication. This weekly injection could be a game-changer for Parkinson’s care,” Prof Garg says.
“Levodopa is the gold-standard therapy for Parkinson’s, but its short life span means it must be taken several times a day.”
UniSA PhD student Deepa Nakmode says the in-situ implant is designed to release both levodopa and carbidopa steadily over one week, maintaining consistent plasma levels and reducing the risks associated with fluctuating drug concentrations.
“After years of focused research, it’s incredibly rewarding to see our innovation in long-acting injectables for Parkinson’s disease reach this stage. Our invention has now been filed for an Australian patent,” Nakmode says.
The injectable gel combines an FDA-approved biodegradable polymer PLGA with Eudragit L-100, a pH-sensitive polymer, to achieve a controlled and sustained drug release.
Extensive lab tests confirmed the system’s effectiveness and safety:
More than 90% of the levodopa dose and more than 81% of the carbidopa dose was released over seven days.
The implant degraded by over 80% within a week and showed no significant toxicity in cell viability tests.
The formulation can be easily administered through a fine 22-gauge needle, minimising discomfort and eliminating the need for surgical implant.
“The implications of this research are profound,” Prof Garg says. “By reducing the frequency of dosing from multiple times a day to a weekly injection is a major step forward in Parkinson’s therapy. We’re not just improving how the drug is delivered; we’re improving patients’ lives.”
Prof Garg says the technology could also be adapted for other chronic conditions such as cancer, diabetes, neurodegenerative disorders, pain management, and chronic infections that require long-term drug delivery.in
The system can be tuned to release drugs over a period ranging from a few days to several weeks depending on therapeutic needs.
UniSA scientists hope to start clinical trials in the near future and are exploring commercialisation opportunities.
Dementia poses a major health challenge with no safe, affordable treatments to slow its progression. Researchers at Lawson Research Institute (Lawson), the research arm of St. Joseph’s Health Care London, are investigating whether Ambroxol – a cough medicine used safely for decades in Europe – can slow dementia in people with Parkinson’s disease.
Published in JAMA Neurology, this 12-month clinical trial involving 55 participants with Parkinson’s disease dementia (PDD) monitored memory, psychiatric symptoms and GFAP, a blood marker linked to brain damage.
Parkinson’s disease dementia causes memory loss, confusion, hallucinations and mood changes. About half of those diagnosed with Parkinson’s develop dementia within 10 years, profoundly affecting patients, families and the health care system.
Led by Cognitive Neurologist Dr Stephen Pasternak, the study gave one group daily Ambroxol while the other group received a placebo.
“Our goal was to change the course of Parkinson’s dementia,” says Pasternak. “This early trial offers hope and provides a strong foundation for larger studies.”
Key findings from the clinical trial include:
Ambroxol was safe, well-tolerated and reached therapeutic levels in the brain.
Psychiatric symptoms worsened in the placebo group but remained stable in those taking Ambroxol.
Participants with high-risk GBA1 gene variants showed improved cognitive performance on Ambroxol.
A marker of brain cell damage (GFAP) increased in the placebo group but stayed stable with Ambroxol, suggesting potential brain protection.
Although Ambroxol is approved in Europe for treating respiratory conditions and has a long-standing safety record – including use at high doses and during pregnancy – it is not approved for any use in Canada or the U.S.
“Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease,” explains Pasternak. “These findings suggest Ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist.”
An old drug with new possibilities
Ambroxol supports a key enzyme called glucocerebrosidase (GCase), which is produced by the GBA1 gene. In people with Parkinson’s disease, GCase levels are often low. When this enzyme doesn’t work properly, waste builds up in brain cells, leading to damage.
Pasternak learned about Ambroxol during a fellowship at The Hospital for Sick Children (SickKids) in Toronto, where it was identified as a treatment for Gaucher disease – a rare genetic disorder in children caused by a deficiency of GCase. He is now applying that research to explore whether boosting GCase with Ambroxol could help protect the brain in Parkinson’s related diseases.
“This research is vital because Parkinson’s dementia profoundly affects patients and families,” says Pasternak. “If a drug like Ambroxol can help, it could offer real hope and improve lives.”
Funded by the Weston Family Foundation, this study is an important step toward developing new treatments for Parkinson’s disease and other cognitive disorders, including dementia with Lewy bodies. Pasternak and his team plan to start a follow-up clinical trial focused specifically on cognition later this year.
What do the brains of newborns and patients with Alzheimer’s disease have in common? Researchers from the University of Gothenburg, led by first author Fernando Gonzalez-Ortiz and senior author Professor Kaj Blennow, recently reported that both newborns and Alzheimer’s patients have elevated blood levels of a protein called phosphorylated tau, specifically a form called p-tau217.
While this protein has been largely used as a diagnostic test for Alzheimer’s disease, with an increase in p-tau217 blood levels proposed to be driven by another process, namely aggregation of b-amyloid protein into amyloid plaques. Newborns (for natural reasons) do not have this type of pathological change, so interestingly, in newborns increased plasma p-tau217 seems to reflect a completely different – and entirely healthy – mechanism.
In a large international study that involved Sweden, Spain and Australia, researchers analyzed blood samples from over 400 individuals, including healthy newborns, premature infants, young adults, elderly adults, and people diagnosed with Alzheimer’s disease. They found that newborn babies had the highest levels of p-tau217 – even higher than those found in people with Alzheimer’s. These levels were particularly elevated in premature babies and started to decrease over the first few months of life, eventually settling to adult levels.
First time in the blood of newborns
Previous research, largely based on animal models, had hinted at the role of phosphorylated tau in early brain development. This is the first time scientists have directly measured p-tau217 concentrations in the blood of human newborns, opening the door to a much clearer understanding of its developmental role.
But here’s where it gets fascinating, while in Alzheimer’s disease p-tau217 is associated with tau aggregation into harmful clumps called tangles, believed to cause the breakdown of brain cells and subsequent cognitive decline. In contrast, in newborns this surge in tau appears to support healthy brain development, helping neurons grow and to form new connections with other neurons, thereby shaping the structure of the young brain.
The study also revealed that in both healthy and premature babies, p-tau217 levels were closely linked to how early they were born. The earlier the birth, the higher the levels of this protein, suggesting a role in supporting rapid brain growth under challenging developmental conditions.
Potential roadmap for new treatments
What’s perhaps most compelling about these findings, published in the journal Brain Communications, is the hint that our brains may once have had built-in protection against the damaging effects of tau, so that newborns can tolerate, and even benefit from, high levels of phosphorylated tau without triggering the kinds of damage seen in Alzheimer’s.
“We believe that understanding how this natural protection works – and why we lose it as we age – could offer a roadmap for new treatments. If we can learn how the newborn brain keeps tau in check, we might one day mimic those processes to slow or stop Alzheimer’s in its tracks”, says Fernando Gonzalez-Ortiz.
So while an increase of p-tau217 is a danger signal in older brains, in newborns it might be a vital part of building one. The same molecule, two dramatically different roles – one building the brain, the other marking its decline.
Plasma p-tau217 has recently received FDA approval for use in diagnosing Alzheimer’s disease, making it an increasingly important tool in clinical settings. The authors emphasise
Source: the need to also understand the mechanism for the increase in p-tau217, especially for interpreting it as an outcome in clinical and epidemiological research and in drug development. This study indicate that amyloid plaques may not be the main driver of increases in p-tau217.
