- Pioneering Biomarker for Resistant Depression Unearthed Neuroscience News
- Cingulate dynamics track depression recovery with deep brain stimulation Nature.com
- Researchers discover biomarker for tracking depression recovery National Institutes of Health (.gov)
- A Newly Discovered Brain Signal Marks Recovery from Depression Scientific American
- Effects of deep brain stimulation on cognitive functioning in treatment-resistant depression: a systematic review and meta-analysis | Molecular Psychiatry Nature.com
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Tag Archives: Biomarker
Researchers discover biomarker for tracking depression recovery – National Institutes of Health (.gov)
- Researchers discover biomarker for tracking depression recovery National Institutes of Health (.gov)
- Cingulate dynamics track depression recovery with deep brain stimulation Nature.com
- A Newly Discovered Brain Signal Marks Recovery from Depression Scientific American
- How AI helped researchers track recovery from depression STAT
- Depression recovery can be hard to measure − new research on deep brain stimulation shows how objective biomarkers could help make treatment more precise The Conversation Indonesia
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Mysteries About Leading Biomarker for Alzheimer’s Solved
Summary: Researchers identify how taupT217, a toxic form of the Tau protein, spreads through the brain as Alzheimer’s disease progresses.
Source: University of Virginia
University of Virginia neuroscientists have revealed how a toxic form of tau protein, notorious for forming tangles in the brains of people with Alzheimer’s disease and several other neurodegenerative disorders, spreads through the brain as the disease progresses.
The tau protein helps cause cognitive decline associated with those diseases. The research shows what provokes its accumulation and how it harms nerve cells called neurons. Scientists may be able to leverage these findings to develop new Alzheimer’s treatments that prevent or delay symptom onset, or slow disease progression once symptoms develop.
UVA’s new research also advances efforts to develop blood tests to detect Alzheimer’s at its earliest stages, when it is, in principle, most amenable to treatment. The researchers found that antibodies used in blood tests for measuring this toxic, chemically modified form of tau, called “taupT217,” can easily be fooled into detecting other proteins, which compromises test accuracy. Fortunately, they also showed how this problem can be avoided.
The new research from UVA’s Dr. George Bloom and collaborators is the most comprehensive examination yet of where and how taupT217 accumulates in the brain. The results provide vital insights into the development of Alzheimer’s and possibly other neurological conditions called “non-Alzheimer’s tauopathies.”
Those include Parkinson’s disease and chronic traumatic encephalopathy.
“The past few years have witnessed exciting advances in early Alzheimer’s detection by measuring the amount of taupT217 in blood or cerebrospinal fluid, but until now almost nothing has been learned about what causes this type of tau to form in the brain or how it affects neuron health,” said Bloom, of UVA’s Departments of Biology, Cell Biology and Neuroscience, as well as the UVA Brain Institute, the Virginia Alzheimer’s Disease Center and UVA’s Program in Fundamental Neuroscience.
“Knowing what provokes taupT217 to build up in the brain and how it harms neurons provides new openings for therapeutic intervention,” he said.
Understanding Alzheimer’s
Tau plays important roles in the healthy brain, where, among other things, it helps build and maintain the “microtubules” that serve as highways for transporting important materials within the neurons that form the brain’s circuitry. But in people with Alzheimer’s, tau becomes chemically modified and misshapen in ways that prevent its normal functioning and make it toxic. This eventually leads to two phenomena that account for cognitive decline in Alzheimer’s: destruction of neuronal circuitry and neuron death.
Why this occurs has been only partially understood, but UVA’s new research offers more answers. For example, the researchers found that they could trigger taupT217 buildup inside cultured neurons by exposing them to clusters, or oligomers, of tau. Those are known to accumulate in the Alzheimer’s brain and have long been suspected as a harmful contributor to the disease.
They also found that the chemical modification that converts normal tau into taupT217 dramatically decreases tau’s ability to stick to microtubules, which in turn may make it easier for the tau to form toxic oligomers.
“In terms of immediate clinical value, we hope that our findings about the challenge of antibody specificity for measuring taupT217 in blood will quickly resonate with companies that are striving to develop commercially available tests to identify Alzheimer’s patients years before symptoms become evident,” Bloom said.
“Because massive irreversible brain damage has already occurred by symptom onset, accurate early diagnosis will be crucial for development of drugs that effectively combat Alzheimer’s.”
That’s just one example of the practical insights generated by UVA’s research that will benefit the efforts to better diagnose and treat Alzheimer’s.
“Alzheimer’s disease reflects a multi-dimensional breakdown of normal brain cells, so there is nothing simple about it,” Bloom said. “Focusing research on the earliest processes that convert normal brains into Alzheimer’s brains, though, provides the best hope for eventually conquering this terrible disease.”
The researchers have published their findings in the journal Alzheimer’s & Dementia. The first author of the paper is Binita Rajbanshi, a recently graduated pharmacology Ph.D. student. The other team members were Anuj Guruacharya, James Mandell and Bloom. The scientists reported that they have no financial interests in the work.
See also
About this Alzheimer’s disease research news
Author: Josh Barney
Source: University of Virginia
Contact: Josh Barney – University of Virginia
Image: The image is in the public domain
Original Research: Open access.
“Localization, induction, and cellular effects of tau phosphorylated at threonine 217 1” by Binita Rajbanshi et al. Alzheimer’s & Dementia
Abstract
Localization, induction, and cellular effects of tau phosphorylated at threonine 217 1
Introduction
Tau phosphorylation at T217 is a promising Alzheimer’s disease (AD) biomarker, but its functional consequences were unknown.
Methods
Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, taupT217, taupT181, taupT231, and taupS396/pS404. Direct stochastic optical reconstruction microscopy (dSTORM) super resolution microscopy was used to localize taupT217 in cultured neurons. Enhanced green fluorescent protein (EGFP)-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules.
Results
In the brain, taupT217 appears in neurons at Braak stages I and II, becomes more prevalent later, and co-localizes partially with other phospho-tau epitopes. In cultured neurons, taupT217 is increased by extracellular tau oligomers (xcTauOs) and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tauT217E.
Conclusion
TaupT217 increases in the brain as AD progresses and is induced by xcTauOs. Post-synaptic taupT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau’s affinity for microtubules.
New Biomarker Can Detect Neurodegeneration in Blood
Neuroscientists have developed a groundbreaking test that can detect a unique marker of Alzheimer’s disease neurodegeneration in a blood sample.
A group of neuroscientists developed a test to detect a novel marker of
“At present, diagnosing Alzheimer’s disease requires neuroimaging,” said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “Those tests are expensive and take a long time to schedule, and a lot of patients, even in the U.S., don’t have access to MRI and PET scanners. Accessibility is a major issue.”
Currently, to diagnose Alzheimer’s disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer’s Association. The guidelines, called the AT(N) Framework, require detection of three distinct components of Alzheimer’s pathology—the presence of amyloid plaques, tau tangles, and neurodegeneration in the brain—either by imaging or by analyzing CSF samples.
Thomas Karikari, Ph.D. Credit: Thomas Karikari
Unfortunately, both approaches suffer from economical and practical limitations, dictating the need for development of convenient and reliable AT(N) biomarkers in blood samples, collection of which is minimally invasive and requires fewer resources. The development of simple tools detecting signs of Alzheimer’s in the blood without compromising on quality is an important step toward improved accessibility, said Karikari.
“The most important utility of blood biomarkers is to make people’s lives better and to improve clinical confidence and risk prediction in Alzheimer’s disease diagnosis,” Karikari said.
Current blood diagnostic methods can accurately detect abnormalities in
By applying their knowledge of molecular biology and biochemistry of tau proteins in different tissues, such as the brain, Karikari and his team, including scientists at the University of Gothenburg, Sweden, developed a technique to selectively detect BD-tau while avoiding free-floating “big tau” proteins produced by cells outside the brain.
To do that, they designed a special antibody that selectively binds to BD-tau, making it easily detectible in the blood. They validated their assay across over 600 patient samples from five independent cohorts, including those from patients whose Alzheimer’s disease diagnosis was confirmed after their deaths, as well as from patients with memory deficiencies indicative of early-stage Alzheimer’s.
The tests showed that levels of BD-tau detected in blood samples of Alzheimer’s disease patients using the new assay matched with levels of tau in the CSF and reliably distinguished Alzheimer’s from other neurodegenerative diseases. Levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue confirmed via brain autopsy analyses.
Scientists hope that monitoring blood levels of BD-tau could improve clinical trial design and facilitate screening and enrollment of patients from populations that historically haven’t been included in research cohorts.
“There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” said Karikari. “To develop better drugs, trials need to enroll people from varied backgrounds and not just those who live close to academic medical centers. A blood test is cheaper, safer and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trial and disease monitoring.”
Karikari and his team are planning to conduct large-scale clinical validation of blood BD-tau in a wide range of research groups, including those that recruit participants from diverse racial and ethnic backgrounds, from memory clinics, and from the community. Additionally, these studies will include older adults with no biological evidence of Alzheimer’s disease as well as those at different stages of the disease. These projects are crucial to ensure that the biomarker results are generalizable to people from all backgrounds, and will pave the way to making BD-tau commercially available for widespread clinical and prognostic use.
Reference: “Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration” by Fernando Gonzalez-Ortiz, Michael Turton, Przemyslaw R Kac, Denis Smirnov, Enrico Premi, Roberta Ghidoni, Luisa Benussi, Valentina Cantoni, Claudia Saraceno and Jasmine Rivolta, 27 December 2022, Brain.
DOI: 10.1093/brain/awac407
Additional authors of this study are Fernando Gonzalez-Ortiz, B.S., Przemyslaw Kac, B.S., Nicholas Ashton, Ph.D., and Henrik Zetterberg, M.D., Ph.D., of the University of Gothenburg, Sweden; Michael Turton, Ph.D., and Peter Harrison, Ph.D., of Bioventix Plc, Farnham, U.K.; Denis Smirnov, B.S., and Douglas Galasko, M.D., of the University of California, San Diego; Enrico Premi, M.D., Valentina Cantoni, Ph.D., Jasmine Rivolta, Ph.D., and Barbara Borroni, M.D., of the University of Brescia, Italy; and Roberta Ghidoni, Ph.D., Luisa Benussi, Ph.D., and Claudia Saraceno, Ph.D., of RCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
This research was supported by the Swedish Research Council (Vetenskåpradet; #2021-03244), the Alzheimer’s Association (#AARF-21-850325), the BrightFocus Foundation (#A2020812F), the International Society for Neurochemistry’s Career Development Grant, the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Swedish Parkinson Foundation (Parkinsonfonden), Gamla Tjänarinnor Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124), the Gun and Bertil Stohnes Foundation and the Anna Lisa and Brother Björnsson’s Foundation, among other sources.
New Biomarker Test Can Detect Alzheimer’s Neurodegeneration in Blood
Summary: A newly developed blood test can detect brain-derived tau (BD-tau), a biomarker of Alzheimer’s disease neurodegeneration.
Source: University of Pittsburgh
A group of neuroscientists led by a University of Pittsburgh School of Medicine researcher developed a test to detect a novel marker of Alzheimer’s disease neurodegeneration in a blood sample.
A study on their results was published today in Brain.
The biomarker, called “brain-derived tau,” or BD-tau, outperforms current blood diagnostic tests used to detect Alzheimer’s-related neurodegeneration clinically. It is specific to Alzheimer’s disease and correlates well with Alzheimer’s neurodegeneration biomarkers in the cerebrospinal fluid (CSF).
“At present, diagnosing Alzheimer’s disease requires neuroimaging,” said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “Those tests are expensive and take a long time to schedule, and a lot of patients, even in the U.S., don’t have access to MRI and PET scanners. Accessibility is a major issue.”
Currently, to diagnose Alzheimer’s disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer’s Association. The guidelines, called the AT(N) Framework, require detection of three distinct components of Alzheimer’s pathology—the presence of amyloid plaques, tau tangles and neurodegeneration in the brain—either by imaging or by analyzing CSF samples.
Unfortunately, both approaches suffer from economical and practical limitations, dictating the need for development of convenient and reliable AT(N) biomarkers in blood samples, collection of which is minimally invasive and requires fewer resources.
The development of simple tools detecting signs of Alzheimer’s in the blood without compromising on quality is an important step toward improved accessibility, said Karikari.
“The most important utility of blood biomarkers is to make people’s lives better and to improve clinical confidence and risk prediction in Alzheimer’s disease diagnosis,” Karikari said.
Current blood diagnostic methods can accurately detect abnormalities in plasma amyloid beta and the phosphorylated form of tau, hitting two of the three necessary checkmarks to confidently diagnose Alzheimer’s.
But the biggest hurdle in applying the AT(N) Framework to blood samples lies in the difficulty of detecting markers of neurodegeneration that are specific to the brain and aren’t influenced by potentially misleading contaminants produced elsewhere in the body.
For example, blood levels of neurofilament light, a protein marker of nerve cell damage, become elevated in Alzheimer’s disease, Parkinson’s and other dementias, rendering it less useful when trying to differentiate Alzheimer’s disease from other neurodegenerative conditions. On the other hand, detecting total tau in the blood proved to be less informative than monitoring its levels in CSF.
By applying their knowledge of molecular biology and biochemistry of tau proteins in different tissues, such as the brain, Karikari and his team, including scientists at the University of Gothenburg, Sweden, developed a technique to selectively detect BD-tau while avoiding free-floating “big tau” proteins produced by cells outside the brain.
To do that, they designed a special antibody that selectively binds to BD-tau, making it easily detectible in the blood. They validated their assay across over 600 patient samples from five independent cohorts, including those from patients whose Alzheimer’s disease diagnosis was confirmed after their deaths, as well as from patients with memory deficiencies indicative of early-stage Alzheimer’s.
The tests showed that levels of BD-tau detected in blood samples of Alzheimer’s disease patients using the new assay matched with levels of tau in the CSF and reliably distinguished Alzheimer’s from other neurodegenerative diseases. Levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue confirmed via brain autopsy analyses.
Scientists hope that monitoring blood levels of BD-tau could improve clinical trial design and facilitate screening and enrollment of patients from populations that historically haven’t been included in research cohorts.
“There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” said Karikari.
“To develop better drugs, trials need to enroll people from varied backgrounds and not just those who live close to academic medical centers. A blood test is cheaper, safer and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trial and disease monitoring.”
Karikari and his team are planning to conduct large-scale clinical validation of blood BD-tau in a wide range of research groups, including those that recruit participants from diverse racial and ethnic backgrounds, from memory clinics, and from the community. Additionally, these studies will include older adults with no biological evidence of Alzheimer’s disease as well as those at different stages of the disease.
These projects are crucial to ensure that the biomarker results are generalizable to people from all backgrounds, and will pave the way to making BD-tau commercially available for widespread clinical and prognostic use.
Additional authors of this study are Fernando Gonzalez-Ortiz, B.S., Przemysław Kac, B.S., Nicholas Ashton, Ph.D., and Henrik Zetterberg, M.D., Ph.D., of the University of Gothenburg, Sweden; Michael Turton, Ph.D., and Peter Harrison, Ph.D., of Bioventix Plc, Farnham, U.K.; Denis Smirnov, B.S., and Douglas Galasko, M.D., of the University of California, San Diego; Enrico Premi, M.D., Valentina Cantoni, Ph.D., Jasmine Rivolta, Ph.D., and Barbara Borroni, M.D., of the University of Brescia, Italy; and Roberta Ghidoni, Ph.D., Luisa Benussi, Ph.D., and Claudia Saraceno, Ph.D., of RCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Funding: This research was supported by the Swedish Research Council (Vetenskåpradet; #2021-03244), the Alzheimer’s Association (#AARF-21-850325), the BrightFocus Foundation (#A2020812F), the International Society for Neurochemistry’s Career Development Grant, the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Swedish Parkinson Foundation (Parkinsonfonden), Gamla Tjänarinnor Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124), the Gun and Bertil Stohnes Foundation and the Anna Lisa and Brother Björnsson’s Foundation, among other sources.
About this Alzheimer’s disease research news
Author: Anastasia Gorelova
Source: University of Pittsburgh
Contact: Anastasia Gorelova – University of Pittsburgh
Image: The image is in the public domain
See also
Original Research: Open access.
“Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration” by Thomas Karikari et al. Brain
Abstract
Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration
Blood-based biomarkers for amyloid beta and phosphorylated tau show good diagnostic accuracies and agreements with their corresponding CSF and neuroimaging biomarkers in the amyloid/tau/neurodegeneration [A/T/(N)] framework for Alzheimer’s disease.
However, the blood-based neurodegeneration marker neurofilament light is not specific to Alzheimer’s disease while total-tau shows lack of correlation with CSF total-tau. Recent studies suggest that blood total-tau originates principally from peripheral, non-brain sources.
We sought to address this challenge by generating an anti-tau antibody that selectively binds brain-derived tau and avoids the peripherally expressed ‘big tau’ isoform. We applied this antibody to develop an ultrasensitive blood-based assay for brain-derived tau, and validated it in five independent cohorts (n = 609) including a blood-to-autopsy cohort, CSF biomarker-classified cohorts and memory clinic cohorts.
In paired samples, serum and CSF brain-derived tau were significantly correlated (rho = 0.85, P < 0.0001), while serum and CSF total-tau were not (rho = 0.23, P = 0.3364). Blood-based brain-derived tau showed equivalent diagnostic performance as CSF total-tau and CSF brain-derived tau to separate biomarker-positive Alzheimer’s disease participants from biomarker-negative controls.
Furthermore, plasma brain-derived tau accurately distinguished autopsy-confirmed Alzheimer’s disease from other neurodegenerative diseases (area under the curve = 86.4%) while neurofilament light did not (area under the curve = 54.3%). These performances were independent of the presence of concomitant pathologies. Plasma brain-derived tau (rho = 0.52–0.67, P = 0.003), but not neurofilament light (rho = −0.14–0.17, P = 0.501), was associated with global and regional amyloid plaque and neurofibrillary tangle counts.
These results were further verified in two memory clinic cohorts where serum brain-derived tau differentiated Alzheimer’s disease from a range of other neurodegenerative disorders, including frontotemporal lobar degeneration and atypical parkinsonian disorders (area under the curve up to 99.6%).
Notably, plasma/serum brain-derived tau correlated with neurofilament light only in Alzheimer’s disease but not in the other neurodegenerative diseases. Across cohorts, plasma/serum brain-derived tau was associated with CSF and plasma AT(N) biomarkers and cognitive function.
Brain-derived tau is a new blood-based biomarker that outperforms plasma total-tau and, unlike neurofilament light, shows specificity to Alzheimer’s disease-type neurodegeneration.
Thus, brain-derived tau demonstrates potential to complete the AT(N) scheme in blood, and will be useful to evaluate Alzheimer’s disease-dependent neurodegenerative processes for clinical and research purposes.
Researchers Pinpoint Important Biomarker for SIDS – Updated
Sudden infant death syndrome (SIDS) accounts for about 37% of sudden unexpected infant deaths a year in the U.S., and the cause of SIDS has remained largely unknown. On Saturday, researchers from The Children’s Hospital Westmead in Sydney released a study that has identified the first biochemical marker that could help detect babies more at risk of SIDS while they are alive.
SIDS refers to the unexplained deaths of infants under a year old, and it usually occurs while the child is sleeping. According to Mayo Clinic, many in the medical community suspected this phenomenon could be caused by a defect in the part of the brain that controls arousal from sleep and breathing. The theory was that if the infant stopped breathing during sleep, the defect would keep them from startling or waking up.
The Sydney researchers were able to confirm this theory by analyzing dried blood samples taken from newborns who died from SIDS and other unknown causes. Each SIDS sample was then compared with blood taken from healthy babies. They found the activity of the enzyme butyrylcholinesterase (BChE) was significantly lower in babies who died of SIDS compared to living infants and other non-SIDS infant deaths. BChE plays a major role in the brain’s arousal pathway, explaining why SIDS typically occurs during sleep.
Previously, parents were told SIDS could be prevented if they only took proper precautions: laying babies on their backs, not letting them overheat and keeping all toys and blankets out of the crib are a few of the most important preventative steps. Importantly, they still are, as there is still no test for this biomarker.
But many children whose parents took every precaution still died from SIDS. These parents were left with immense guilt, wondering if they could have prevented their baby’s death.
Dr. Carmel Harrington, the lead researcher for the study, was one of these parents. Her son unexpectedly and suddenly died as an infant 29 years ago. In an interview with the Australian Broadcasting Corporation (ABC), Harrington explained what she was told about the cause of her child’s death.
“Nobody could tell me. They just said it’s a tragedy. But it was a tragedy that didn’t sit well with my scientific brain.”
Since then, she’s worked to find the cause of SIDS, both for herself and for the medical community as a whole. She went on to explain why this discovery is so important for parents whose babies suffered from SIDS.
“These families can now live with the knowledge that this was not their fault,” she said.
In the study, the researchers wrote, “This finding represents the possibility for the identification of infants at risk for SIDS infants prior to death and opens new avenues for future research into specific interventions.”
Now that this biomarker has been further confirmed, researchers can turn their attention to a solution. In the next few years, those in the medical community who have studied SIDS will likely work on a screening test to identify babies who are at risk for SIDS and hopefully prevent it altogether.
BioSpace would like to clarify that despite this breakthrough, it is still abundantly important that anyone caring for a baby should follow safe sleeping practices. Ie: laying them on their backs, not letting them overheat and keeping all toys and blankets out of the crib. We are in contact with Dr. Harrington and look forward to a more in-depth discussion on the potential implications of these findings.
SIDS breakthrough? Possible sudden infant death syndrome biomarker identified
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Babies at risk for sudden infant death syndrome (SIDS) could be identified through a biochemical marker, a new study published in The Lancet’s eBioMedicine finds.
SIDS is the unexplained death of a seemingly healthy baby less than a year old, typically during sleep, according to the Mayo Clinic. The CDC reports SIDS accounted for 37% of infant deaths in the United States in 2019.
Researchers investigating the cause of SIDS at the Children’s Hospital at Westmead (CHW) in Australia said they identified the first biochemical marker that could help detect babies more at risk of sudden infant death syndrome while they are still alive.
Dr. Carmel Harrington, an honorary research fellow who led the study, said its findings were game-changing. Harrington said the study provided an explanation for SIDS and hope for prevention of deaths associated with this mysterious condition.
“An apparently healthy baby going to sleep and not waking up is every parent’s nightmare and until now there was absolutely no way of knowing which infant would succumb. But that’s not the case anymore. We have found the first marker to indicate vulnerability prior to death,” Harrington said in a news release.
Doctors are cheering a potential breakthrough in the mystery of sudden infant death syndrome (SIDS).
(iStock, File)
BABY BRANDON KIDNAPPING SUSPECTS TRIED TO ABDUCT THE INFANT ON THREE PREVIOUS OCCASSIONS, PROSECUTORS SAY
According to the study, the Australian researchers analyzed levels of a specific enzyme called butyrylcholinesterase (BChE), in 722 dried blood spots (DBS) taken at birth as part of a newborn screening program. They measured levels of BChE in infants dying from SIDS and from other causes, each compared to 10 surviving infants with the same date of birth and gender.
The investigators found lower levels of BChE in babies who died from SIDS compared to living control groups of infants and other non-SIDS-related infant deaths, according to the published report.
“We conclude that a previously unidentified cholinergic deficit, identifiable by abnormal -BChEsa, is present at birth in SIDS babies and represents a measurable, specific vulnerability prior to their death,” the researchers stated.
The SIDS study could move investigators closer to solving the health mystery.
(iStock, File)
The researchers explained that BChE plays a vital role in the brain’s arousal pathway. They further explained that a deficiency in BChE likely suggests an arousal deficit in babies, which would reduce their abilities to wake or respond to the external environment, making them susceptible to SIDS.
“Babies have a very powerful mechanism to let us know when they are not happy. Usually, if a baby is confronted with a life-threatening situation, such as difficulty breathing during sleep because they are on their tummies, they will arouse and cry out. What this research shows is that some babies don’t have this same robust arousal response,” Harrington said.
WHO REPORTS COVID CASES DOWN EVERYWHERE BUT AFRICA, AMERICAS
A doctor noted the study’s sample size was limited.
(iStock, File)
Dr. Matthew Harris, an emergency medicine pediatrician at Cohen Children’s Medical Center/ Northwell Health on Long Island, New York, was not involved with the study but told Fox News, “The findings of the study are interesting and important. While the sample size is limited, the study seems to indicate that lower levels of this enzyme are associated with a higher risk for sudden infant death syndrome. Importantly, this might present an opportunity for both earlier screening for risk factors during the perinatal period, and might offer scientists and physicians an opportunity to discover an intervention.”
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Harris added, “Currently, we screen for dozens of metabolic disorders as part of the newborn screening process, and if this proves to be a real association, this may add to the growing list of disorders we can detect early and possibly prevent the progression to severe disease.”
Harrington, who not only led the study but also experienced the loss of her own baby to SIDS nearly three decades ago, said in the news release that until now, health experts were not aware of what caused the lack of arousal in infants. “Now that we know that BChE is involved we can begin to change the outcome for these babies and make SIDS a thing of the past.”
Warning About Brain-Boosting Supplements After Alzheimer’s Disease Biomarker Discovery
Elevated levels of an enzyme called PHGDH in the blood of older adults could be an early warning sign of
Researchers led by Sheng Zhong, a professor of bioengineering at the UC San Diego Jacobs School of Engineering, and Xu Chen, a professor of neurosciences at UC San Diego School of Medicine, published their findings on May 3, 2022, in the journal Cell Metabolism.
The new study builds on earlier work by Zhong and colleagues that first identified PHGDH as a potential blood biomarker for Alzheimer’s disease. The researchers had analyzed blood samples of older adults and found a steep increase in PHGDH gene expression in Alzheimer’s patients, as well as in healthy individuals approximately two years before they were diagnosed with the disease.
The results were promising, and the researchers were curious if this increase could be linked back to the brain. In their new study, they show that this indeed is the case.
“It’s exciting that our previous discovery of a blood biomarker is now corroborated with brain data,” said Zhong. “Now we have strong evidence that the changes we see in human blood are directly correlated to changes in the brain in Alzheimer’s disease.”
The researchers analyzed genetic data collected from post-mortem human brains from subjects in four different research cohorts, each made up of 40 to 50 individuals 50 years and older. The subjects consisted of Alzheimer’s patients, so-called “asymptomatic” individuals (people without cognitive problems and without an Alzheimer’s diagnosis, but whose post-mortem brain analyses showed early signs of Alzheimer’s-related changes), and healthy controls.
The results showed a consistent increase in PHGDH expression among Alzheimer’s patients and asymptomatic individuals in all four cohorts compared to the healthy controls. Moreover, expression levels were higher the more advanced the disease. This trend was also observed in two different mouse models of Alzheimer’s disease.
The researchers also compared the subjects’ PHGDH expression levels with their scores on two different clinical assessments: the Dementia Rating Scale, which rates a person’s memory and cognitive ability, and Braak staging, which rates the severity of Alzheimer’s disease based on the brain’s pathology. The results showed that the worse the scores, the higher the expression of PHGDH in the brain.
“The fact that this gene’s expression level directly correlates with both a person’s cognitive ability and disease pathology is remarkable,” said Zhong. “Being able to quantify both of these complex metrics with a single molecular measurement could potentially make diagnosis and monitoring progression of Alzheimer’s disease much simpler.”
The case against serine
The findings come with implications for serine supplements, which are advertised to improve memory and cognitive function. The key player responsible for making serine in the body is PHGDH. Some researchers have proposed that PHGDH expression is reduced in Alzheimer’s disease, and that boosting serine intake could help with treatment and prevention. Clinical trials are already underway to test serine treatments in older adults experiencing cognitive decline.
But with their data consistently showing increased PHGDH expression in Alzheimer’s, the researchers posit that serine production may likely be increased in this disease, contrary to what some other groups claim.
“Anyone looking to recommend or take serine to mitigate Alzheimer’s symptoms should exercise caution,” said co-first author Riccardo Calandrelli, who is a research associate in Zhong’s lab.
Next steps
The researchers are looking to study how changing PHGDH gene expression will affect disease outcomes. The approach could lead to new therapeutics for Alzheimer’s.
A San Diego-based biotechnology startup co-founded by Zhong, called Genemo, is working to develop a PHGDH blood test for early detection of Alzheimer’s disease.
Reference: “PHGDH expression increases with progression of Alzheimer’s disease pathology and symptoms” by Xu Chen, Riccardo Calandrelli, John Girardini, Zhangming Yan, Zhiqun Tan, Xiangmin Xu, Annie Hiniker and Sheng Zhong, 3 May 2022, Cell Metabolism.
DOI: 10.1016/j.cmet.2022.02.008
This work is partially funded by the National Institutes of Health (grant UG3CA256960) and a Kruger Research Award. The authors thank the University of California Alzheimer’s Disease Research Centers at UC Irvine (funded by NIH grant P50AG16573) and UC San Diego (funded by NIH grant P30AG062429) for providing postmortem tissue samples.
New Alzheimer’s Biomarker May Facilitate Rapid Diagnosis
Summary: The discovery of a unique ratio of metabolites in blood samples taken from early-stage Alzheimer’s patients could be a critical new biomarker for early detection of the neurodegenerative disease.
Source: Brain Chemistry Labs
Although symptoms of advanced Alzheimer’s disease are well known, diagnosis of Alzheimer’s disease in its earliest stages requires careful cognitive testing by neurologists.
Discovery of a unique ratio of metabolites from blood samples of early-stage Alzheimer’s patients promises to speed diagnosis, allowing earlier treatments to be initiated.
“We were delighted to discover that the ratio of two molecules, 2-aminoethyl dihydrogen phosphate and taurine, allows us to reliably discriminate samples of early-stage Alzheimer’s patients from controls,” said Dr. Sandra Banack, lead author of the report in PLOS ONE and Senior Scientist at the Brain Chemistry Labs in Jackson Hole.
The blood samples were drawn from patients enrolled in an FDA-approved Phase II trial at Dartmouth Hitchcock Medical Center in New Hampshire and then shipped to the Brain Chemistry Labs for analysis.
Current attempts to diagnose Alzheimer’s disease from blood samples depend on the presence of amyloid fragments, the molecules that cause brain tangles and plaques.
“At the Brain Chemistry Labs, we consider amyloid plaques to be a consequence rather than the cause of Alzheimer’s disease,” Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs explains.
“What is exciting about this new discovery is that it does not depend on amyloid and the assay can be performed on analytical equipment that is already present in most large hospitals.”
About this Alzheimer’s disease research news
Author: Marilyn Asay
Source: Brain Chemistry Labs
Contact: Marilyn Asay – Brain Chemistry Labs
Image: The image is in the public domain
Original Research: Open access.
“A Possible Blood Plasma Biomarker for Early-stage Alzheimer’s Disease” by Sandra Banack et al. PLOS ONE
Abstract
A Possible Blood Plasma Biomarker for Early-stage Alzheimer’s Disease
See also
We sought to identify a usable biomarker from blood samples to characterize early-stage Alzheimer’s disease (AD) patients, in order to facilitate rapid diagnosis, early therapeutic intervention, and monitoring of clinical trials.
We compared metabolites from blood plasma in early-stage Alzheimer’s disease patients with blood plasma from healthy controls using two different analytical platforms: Amino Acid Analyzer and Tandem Mass-Spectrometer.
Early-stage Alzheimer’s patient blood samples were obtained during an FDA-approved Phase IIa clinical trial (Clinicaltrial.gov NCT03062449). Participants included 25 early-stage Alzheimer’s patients and 25 healthy controls in the United States.
We measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples.
We found that plasma concentrations of a phospholipid metabolite, 2-aminoethyl dihydrogen phosphate, normalized by taurine concentrations, distinguish blood samples of patients with early-stage AD.
This possible new Alzheimer’s biomarker may supplement clinical diagnosis for early detection of the disease.
First ‘Before-and-After’ COVID Brain Imaging Study Shows Changes
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
Even mild cases of COVID-19 are associated with brain changes including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers write.
The findings were published online today in the journal Nature.
Gray Matter Loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK.
They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans to image distinct regions of the brain and brain function.
Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula — all of which are largely involved in the sense of smell.
Participants who had contracted COVID also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More Research Needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ ” Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release.
“The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Taquet has collaborated previously with some of the investigators.
Nature. Published online March 8, 2022. Abstract
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