Tag: Parkinson's Disease

Categories : Neurodegenerative Diseases NeurologyTags :

Autism Linked to Elevated Risk of Parkinson’s Disease

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Photo by Robina Weermeijer on Unsplash

People with an autism diagnosis are at a higher risk of developing Parkinson’s disease early in life, according to a large-scale study from Karolinska Institutet. The researchers believe that the two conditions can share underlying biological mechanisms.

The study, published in JAMA Neurology, is based on registry data from over two million people born in Sweden between 1974 and 1999 who were followed from the age of 20 up to the end of 2022.

The researchers interrogated a possible connection between the neuropsychiatric diagnosis Autism Spectrum Disorder (ASD), which affects an individual’s thought processes, behaviour and interpersonal communication, and early-onset Parkinson’s disease, a condition that affects locomotion and movement.

Possible dopamine involvment

The results show that people with an autism diagnosis were four times more likely to develop Parkinson’s disease than people without such a diagnosis, a correlation that remained when controlling for socioeconomic status, a genetic predisposition for mental illness or Parkinson’s disease and other such factors.

“This indicates that there can be shared biological drivers behind ASD and Parkinson’s disease,” says first author Weiyao Yin at the Department of Medical Epidemiology and Biostatistics. “One hypothesis is that the brain’s dopamine system is affected in both cases, since the neurotransmitter dopamine plays an important part in social behaviour and motion control.”

It is well-known that dopamine-producing neurons are degraded in Parkinson’s disease. Previous studies have also shown that dopamine is possibly implicated in autism, but more research needs to be done to confirm this.

“We hope that our results will eventually help to bring greater clarity to the underlying causes of both ASD and Parkinson’s disease,” says Dr Yin.

Medical checkups are vital

Depression and the use of antidepressants are common in people with autism, as are antipsychotic drugs, which are known for being able to cause Parkinson’s-like symptoms. When the researchers adjusted for these factors, the correlation between ASD and the later development of Parkinson’s disease was less salient, but the risk was still double.

The researchers point out that they only analysed early-onset Parkinson’s disease before the age of 50 and that the average age of participants by the end of the study was 34. The incidence of Parkinson’s disease was therefore very low. Future studies will need to examine if the elevated risk persists into older age. 

“The healthcare services need to keep people with ASD – a vulnerable group with high co-morbidity and a high use of psychotropics – under long-term observation,” says last author Sven Sandin, statistician and epidemiologist at the Department of Medical Epidemiology and Biostatistics. “At the same time, it’s important to remember that a Parkinson’s diagnosis before the age of 50 is very rare, including for people with autism.”

Source: Karolinska Institutet

Categories : Implants and Prostheses Neurodegenerative DiseasesTags :

Unlocking New Areas of the Brain for Stimulation in Parkinson’s

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Deep brain stimulation illustration. Credit: NIH

People with Parkinson’s disease increasingly lose their mobility over time and are eventually unable to walk. Hope for these patients rests on deep brain stimulation. In a recent study, researchers at Ruhr University Bochum and Philipps-Universität Marburg, Germany, investigated whether and how stimulation of a certain region of the brain can have a positive impact on ambulatory ability and provide patients with a better quality of life. To do so, the researchers used a technique in which the nerve cells are activated and deactivated via light. Their report appeared in the journal Scientific Reports.

Improving ambulatory ability

If medication is no longer sufficient in alleviating restricted mobility in the advanced stage of Parkinson’s disease, one alternative is deep brain stimulation. An electrical pulse emitter is implanted within the brain, such as in the subthalamic nucleus, which is functionally part of the basal ganglia system. 

The group under Dr Liana Melo-Thomas from Philipps-Universität Marburg was able to show in previous studies on rats that stimulation of the inferior colliculus, chiefly known for processing auditory input, can be used to overcome mobility restrictions. “There are indications that stimulation of this region of the brain leads to activation of the mesencephalic locomotor region, or MLR,” says Melo-Thomas.

Interestingly, the colliculus inferior – unlike the basal ganglia –is not affected by Parkinson’s disease. However, the research group under Melo-Thomas discovered that its stimulation activates alternative motor pathways and can improve patients’ mobility.

The current study aimed to further investigate this activating influence of the inferior colliculus on the MLR. “We suspected that this would have a positive effect on ambulatory ability,” says Melo-Thomas.

Optically influencing nerve cells

The Marburg group led by Professor Rainer Schwarting sought support by Dr Wolfgang Kruse from the Department of General Zoology and Neurobiology at Ruhr University Bochum. The team in Bochum led by Professor Stefan Herlitze played a significant role in co-developing the methods of optogenetics.

While doing so, the researchers ensure that the nerve cells of genetically modified test animals produce a light-sensitive protein in interesting regions of the brain. Light that reaches these nerve cells via small, implanted optical fibres allows the researchers to activate or inhibit them specifically. “This method is thus much more precise than electrical stimulation, which always affects the area around the cells as well,” says Kruse.

For the first time, the effect of the stimulation was directly documented with electrophysiological measurements of neuronal activity in the target structures. A multi-electrode system originally developed at Philipps-Universität Marburg was used for this purpose. By combining these methods, the researchers were able to directly understand the effect of the stimulation. Parallel measurement with up to four electrodes is also highly efficient, allowing minimisation of the number of animals used. Behavioural effects that can be triggered by the stimulation were monitored in conscious animals.

Stimulation of the inferior colliculus provides the desired effect

Optogenetic stimulation in the inferior colliculus predominantly triggered the expected increase in neuronal activity within it. “Simultaneous measurements in the deeper MLR region showed increased activity in the majority of cells, although nearly one quarter of the cells were inhibited by the additional activity in the inferior colliculus,” reports Kruse. The activation of individual nerve cells occurred with an average delay of 4.7 milliseconds, indicating a functional synaptic interconnection between the inferior colliculus and MLR.

Foundations for new types of therapy

Investigating circuits outside of the basal ganglia that are affected by Parkinson’s disease is a promising step in the search for a new therapeutic approach to alleviating motor deficits resulting from the disease. Such is the case with the connection between the inferior colliculus and the MLR that was investigated for this study.

“Even if the path toward new therapeutic approaches to alleviating the symptoms of Parkinson’s disease still appears long, such foundational research is immensely important,” emphasises Kruse. The exact mechanisms that lead to the observed relief of symptoms with deep brain stimulation in the basal ganglia are not fully understood. Further investigation of the underlying interconnections may provide new insight that could optimise therapy in the long term.

Source: Ruhr-University Bochum

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

New Biomarker for Parkinson’s Disease Discovered in CSF

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A misfolded protein facilitates reliable diagnosis even in the early stages of Parkinson’s disease in body fluids.

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Parkinson’s disease is a neurodegenerative disorder that is usually diagnosed in its late stage on the basis of clinical symptoms, mainly motor disorders. By this point, however, the brain is already severely and irreparably damaged. Moreover, diagnosis is difficult and often incorrect because the disease takes many forms and symptoms overlap with other disorders.

Researchers from the PRODI Center for Protein Diagnostics at Ruhr University Bochum, Germany, and the biotech company betaSENSE have now discovered a biomarker in cerebrospinal fluid (CSF) that facilitates a reliable diagnosis at an early stage and can shed light on the progression of the disease and the effect of a therapy. They report their findings in the journal EMBO Molecular Medicine.

Parkinson’s disease – an unstoppable condition

Parkinson’s disease is characterised by the loss of dopaminergic nerve cells in the brain, typically leading to increasing motor impairments as the symptoms progress. Dopamine supplements can compensate for the loss and temporarily alleviate the symptoms. The misfolding of the key protein alpha-synuclein (αSyn) from α-helical structures to β-sheet-rich structures plays a crucial role in the development of Parkinson’s disease. “These misfoldings make the protein sticky, leading to the formation of larger complexes, so-called oligomers. The oligomers then produce long fibrillar filaments and cause the aggregation of these filaments into macroscopically large Lewy bodies in the brain,” explains Professor Klaus Gerwert, founding and managing director at PRODI and CEO of betaSENSE.

Advanced platform technology

In two independent clinical cohorts with a total of 134 participants, the Bochum-based researchers showed that, with a sensitivity and specificity of well over 90%, this misfolding of αSyn in body fluids is a viable biomarker for the diagnosis of Parkinson’s disease. The research was conducted using cerebrospinal fluid samples from patients at the Parkinson’s centres in Bochum (St. Josef Hospital, Professor Lars Tönges, Professor Ralf Gold) and Kassel (Paracelsus-Elena-Klinik, Dr. Sandrina Weber, Professor Brit Mollenhauer). The measurements were carried out using the patented iRS (immuno-infrared sensor) technology from betaSENSE GmbH.

betaSENSE has already successfully implemented the iRS technology for diagnosing Alzheimer’s disease. In this case, it was shown that the misfolding of the biomarker Aβ can indicate the risk of Alzheimer’s dementia at a later stage with high accuracy up to 17 years before clinical diagnosis. “We have now transferred this approach to Parkinson’s for the misfolding of αSyn,” stresses Klaus Gerwert.

Development of Parkinson’s drugs

In addition to diagnostic applications, the technology can also help to develop new active substances and prove their efficacy in clinical trials.

Source: Ruhr-University Bochum

Categories : Neurodegenerative Diseases NeurologyTags :

Head Trauma may Activate Latent Viruses, Leading to Neurodegeneration

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In sports, the connection between head injuries and neurodegenerative diseases such as chronic traumatic encephalopathy, Alzheimer’s disease, and Parkinson’s disease is now well recognised.

Researchers at Tufts University and Oxford University have now uncovered mechanisms that may connect the dots between trauma events and the emergence of disease. They point to latent viruses lurking in most of our brains that may be activated by the jolt, leading to inflammation and accumulating damage that can occur over the ensuing months and years. 

The results suggest the use of antiviral drugs as potential early preventive treatments post-head injury. The findings are published in a study in Science Signaling.

The microbiome aids in digestion, immune system development, and protection against harmful pathogens. 

But the microbiome also includes dozens of viruses that swarm within our bodies at any given time. Some of these can be potentially harmful, but simply lie dormant within our cells. Herpes simplex virus 1 (HSV-1), found in over 80% of people, and varicella-zoster virus, found in 95% of people, are known to make their way into the brain and sleep within our neurons and glial cells.

Dana Cairns, GBS12, research associate in the Department of Biomedical Engineering and lead author of the study, had found evidence in earlier studies suggesting that activation of HSV-1 from its dormant state triggers the signature symptoms of Alzheimer’s disease in lab models of brain tissue: amyloid plaques, neuronal loss, inflammations, and diminished neural network functionality.

“In that study, another virus – varicella – created the inflammatory conditions that activated HSV-1,” said Cairns. “We thought, what would happen if we subjected the brain tissue model to a physical disruption, something akin to a concussion? Would HSV-1 wake up and start the process of neurodegeneration?”

The link between HSV-1 and Alzheimer’s disease was first suggested by co-author Ruth Itzhaki, visiting professorial fellow at Oxford University, who more than 30 years ago identified the virus in a high proportion of brains from the elderly population. Her subsequent studies suggested that the virus can be reactivated in the brain from a latent state by events such as stress or immunosuppression, ultimately leading to neuronal damage.

Blows to Brain-like Tissue

In the current study, the researchers used a lab model that reconstructs the environment of the brain to better understand how concussions may set off the first stages of virus reactivation and neurodegeneration.

The brain tissue model consists of a 6mm-wide donut-shaped sponge-like material made of silk protein and collagen suffused with neural stem cells, which are then coaxed into mature neurons, growing axons and dendrite extensions and forming a network. Glial cells also emerge from the stem cells to help mimic the brain environment and nurture the neurons.

The neurons communicate with each other through their extensions similarly to how they would communicate in a brain. And just like cells in the brain, they can carry within them the DNA of dormant HSV-1 virus.  

After enclosing the brain-like tissue in a cylinder and giving it a sudden jolt atop a piston, mimicking a concussion, Cairns examined the tissue under the microscope over time. Some of the tissue models had neurons with HSV-1, and some were virus-free. 

Following the controlled blows, she observed that the infected cells showed re-activation of the virus, and shortly after that the signature markers of Alzheimer’s disease, including amyloid plaques, p-tau (a protein that creates fiber-like “tangles” in the brain), inflammation, dying neurons, and a proliferation of glial cells called gliosis.

More strikes with the pistons on the tissue models mimicking repetitive head injuries led to the same reactions, which were even more severe. Meanwhile, the cells without HSV-1 showed some gliosis, but none of the other markers of Alzheimer’s disease.

The results were a strong indicator that athletes suffering concussions could be triggering reactivation of latent infections in the brain that can lead to Alzheimer’s disease. Epidemiological studies have shown that multiple blows to the head can lead to doubling or even greater chances of having a neurodegenerative condition months or years down the line.
 
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks, and lower the risk of Alzheimer’s disease,” said Cairns.

The problem goes far beyond the concerns for athletes. Traumatic brain injury is one of the most common causes of disability and death in adults, affecting about 69 million people worldwide each year, at an economic cost estimated at $400 billion annually.

“The brain tissue model takes us to another level in investigating these connections between injury, infection, and Alzheimer’s disease,” said David Kaplan, Stern Family Endowed Professor of Engineering at Tufts.

“We can re-create normal tissue environments that look like the inside of a brain, track viruses, plaques, proteins, genetic activity, inflammation and even measure the level of signalling between neurons,” he said. “There is a lot of epidemiological evidence about environmental and other links to the risk of Alzheimer’s. The tissue model will help us put that information on a mechanistic footing and provide a starting point for testing new drugs.”

Source: Tufts University

Categories : Neurodegenerative DiseasesTags :

Hearing Impairment may be a Sign of Increased Risk of Parkinson’s Disease

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Photo by JD Mason on Unsplash

There may be a link between hearing impairment and an increased risk of developing Parkinson’s according to research led by Lancaster University. This is one of the first studies to examine whether sensory impairments, such as hearing loss, might increase the risk for Parkinson’s or serve as an early warning sign.

The study is published in Parkinsonism and Related Disorders.

Researchers analysed data from the UK Biobank, a biomedical database containing data from half a million participants across the UK. They looked at data from 159,395 individuals who had previously undergone a hearing test measuring their ability to detect speech in noisy environments and had no history of Parkinson’s at the time of the assessment.

Over an average follow-up period of 14.24 years, 810 participants were subsequently diagnosed with Parkinson’s disease. The analysis revealed a 57% increased risk of Parkinson’s for every 10-decibel increase in baseline hearing impairment.

Dr Megan Readman, ESRC Post Doctoral Research Fellow from Lancaster University’s Department of Psychology, led the study.

She said: “These findings are incredibly important; first, this is one of the first studies to look at how hearing impairments may increase risk for Parkinson’s or be an early warning sign of Parkinson’s.

“Secondly, as our findings suggest, hearing loss is intricately related to Parkinson’s so it may be beneficial for auditory functioning and the management of auditory impairment to be considered at the time of diagnosis and follow-up care.”

However, Dr Readman stressed that it is not clear if the link between Parkinson’s and hearing loss is causal or if there is simply a correlation.

“We do not know whether hearing loss can cause Parkinson’s, or if there is a common underlying cause for both conditions.”

The other authors included Yang Wang and Fang Wan, Sally Linkenauger, Trevor Crawford and Christopher Plack plus Ian Fairman who has Parkinson’s and hearing impairment.

Professor Plack said: “It is increasingly clear that hearing loss is not an isolated condition but is associated with several other disorders. Understanding these links is vital if we are to provide effective patient care, improving independence and quality of life for the individuals concerned.”

By identifying factors that might contribute to its onset, such as hearing impairment, researchers hope to pave the way for new strategies in prevention and care.

Dr Readman said: “Our findings suggest hearing impairment is intricately related to Parkinson’s and underscore the potential benefits of addressing auditory function in Parkinson’s diagnosis and follow-up care.”

Professor Trevor Crawford said: “This important study is the latest discovery in a decade-long series of research on neurodegenerative disorders, conducted by our team at Lancaster University in collaboration with colleagues across the UK.”

Source: Lancaster University

Categories : Gastrointestinal Neurodegenerative DiseasesTags :

Parkinson’s Drug Found to Promote Pathogenic Gut Bacteria

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Fig. 1: Chemical imaging of active gut microbes. After brief incubation with heavy water, culture medium and a drug, various chemical bonds (here C-D and C-H) in the stool sample are shown in yellow and green, their ratio in yellow-purple (left). Selected microbes are detected in the same image section with fluorescence-labelled oligonucleotide probes in cyan. The activity of the detected microbes can be determined based on the amount of C-D bonds. C: Xiaowei Ge (Boston University)

An international team of scientists have revealed that the widely prescribed Parkinson’s disease drug entacapone significantly disrupts the human gut microbiome by inducing iron deficiency. This international study, provides new insights into the often-overlooked impact of human-targeted drugs on the microbial communities that play a critical role in human health. The findings, published in Nature Microbiology, suggest however that iron supplementation can help counteract these impacts.

While it is well established that antibiotics can significantly disrupt the human gut microbiome, emerging research shows that a wide range of human-targeted drugs – particularly those used to treat neurological conditions – can also profoundly affect the microbial communities living in our bodies. Despite their intended therapeutic effects on different organs, these drugs can inadvertently disrupt the balance of gut microbes, leading to potential health consequences. Until now, most studies investigating these interactions relied either on patient cohort analyses affected by many confounding factors or on experiments using isolated gut bacteria, which do not fully capture the complexity of the human microbiome.

Investigating drug–bug interactions

The team, which included some from the University of Vienna, used a novel experimental approach. The researchers studied the effects of two drugs – entacapone and loxapine, a medication for schizophrenia – on faecal samples from healthy human donors. They incubated the samples with therapeutic concentrations of these drugs, then analysed the impact on the microbial communities using advanced molecular and imaging techniques, including heavy water labelling combined with Stimulated Raman Spectroscopy (SRS). The team discovered that loxapine and even more so entacapone severely inhibited many microbiome members, while E. coli dramatically expanded in the presence of entacapone.

“The results were even more striking when we examined microbial activity, rather than just their abundance,” explained Fatima Pereira, lead author of the study and former Postdoctoral researcher at the University of Vienna. “The heavy water-SRS method allowed us to observe the subtle yet significant changes in the gut microbiome, which are often missed in traditional abundance-based measurements.”

Entacapone induces iron starvation, favours pathogenic microbes

The researchers hypothesised that entacapone might interfere with iron availability in the gut, a crucial resource for many microbes. Their experiments confirmed that adding iron to faecal samples containing entacapone counteracted the drug’s microbiome-altering effects. Further investigation revealed that E. coli, which thrived under these conditions, carried a highly efficient iron-uptake system (enterobactin siderophore). This system allowed the bacteria to overcome iron starvation and proliferate, even in the presence of the drug.

“By showing that entacapone induces iron deficiency, we have uncovered a new mechanism of drug-induced gut dysbiosis, in which the drug selects for E. coli and other potentially pathogenic microbes well adapted to iron limiting conditions,” said Michael Wagner, scientific director of the Excellence Cluster and vice-head of the Centre for Microbiology and Environmental Systems Science (CeMESS) at the University of Vienna.

Wider implications for drug–microbiome interactions

This discovery has broader implications for understanding how other human-targeted drugs might affect the gut microbiome. Several drugs, including entacapone, contain metal-binding catechol groups, suggesting that this mechanism could be a more common pathway for drug-induced microbiome alterations.

The findings also present an opportunity to mitigate the side effects of drugs like entacapone. By ensuring sufficient iron availability to the large intestine, it may be possible to reduce dysbiosis and the gastrointestinal issues that often accompany Parkinson’s disease treatment.

“The next step is to explore how we can modify drug treatments to better support the gut microbiome,” said Wagner. “We are looking at strategies to selectively deliver iron to the large intestine, where it can benefit the microbiome without interfering with drug absorption in the small intestine.”

Source: University of Vienna

Categories : Neurodegenerative Diseases NeurologyTags :

Major Discovery for the Understanding of Parkinson’s Disease: New Neurotransmitter

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Neurotransmitters at a synapse. Credit: Scientific Animations CC4.0

The treatment of certain neurodegenerative diseases and the pages of neuroscience textbooks may soon be in need of a major update. A research team has discovered that a molecule in the brain – ophthalmic acid – unexpectedly acts like a neurotransmitter similar to dopamine in regulating motor function, offering a new therapeutic target for Parkinson’s and other movement diseases.

As reported in the journal Brain, researchers observed that ophthalmic acid binds to and activates calcium-sensing receptors in the brain, reversing the movement impairments of Parkinson’s mouse models for more than 20 hours.

Parkinson’s disease (PD) symptoms, which include tremors, shaking and lack of movement, are caused by decreasing levels of dopamine in the brain as those neurons die. L-dopa, the front-line drug for treatment, acts by replacing the lost dopamine and has a duration of two to three hours. While initially successful, the effect of L-dopa fades over time, and its long-term use leads to dyskinesia – involuntary, erratic muscle movements in the patient’s face, arms, legs and torso.

“Our findings present a groundbreaking discovery that possibly opens a new door in neuroscience by challenging the more-than-60-year-old view that dopamine is the exclusive neurotransmitter in motor function control,” said co-corresponding author Amal Alachkar, School of Pharmacy & Pharmaceutical Sciences professor. “Remarkably, ophthalmic acid not only enabled movement, but also far surpassed L-dopa in sustaining positive effects. The identification of the ophthalmic acid-calcium-sensing receptor pathway, a previously unrecognised system, opens up promising new avenues for movement disorder research and therapeutic interventions, especially for Parkinson’s disease patients.”

Alachkar began her investigation into the complexities of motor function beyond the confines of dopamine more than two decades ago, when she observed robust motor activity in Parkinson’s mouse models without dopamine. In this study, the team conducted comprehensive metabolic examinations of hundreds of brain molecules to identify which are associated with motor activity in the absence of dopamine. After thorough behavioural, biochemical and pharmacological analyses, ophthalmic acid was confirmed as an alternative neurotransmitter.

“One of the critical hurdles in Parkinson’s treatment is the inability of neurotransmitters to cross the blood-brain barrier, which is why L-DOPA is administered to patients to be converted to dopamine in the brain,” Alachkar said. “We are now developing products that either release ophthalmic acid in the brain or enhance the brain’s ability to synthesise it as we continue to explore the full neurological function of this molecule.”

Source: University of California – Irvine

Categories : Ethics and Law Neurodegenerative DiseasesTags :

Over 100 Key Alzheimer’s Papers Found To Have Suspicious Data

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An investigation by Science has shown that over 100 key papers on Alzheimer’s research have used falsified data. The papers all have a common author – veteran neuropathologist Eliezer Masliah, a key researcher at the National Institute on Aging (NIA), typically as first or last author.

The investigation has found that scores of Masliah’s lab studies at the University of California San Diego (UCSD) and NIA are riddled with apparently falsified Western blots (images used to show the presence of proteins) and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, under supposedly different experimental conditions.

At UCSD, Masliah had amassed decades of experience researching Alzheimer’s and Parkinson’s disease, amassing 800 papers. Some important topics in them, such as alpha-synuclein (a protein linked to both diseases), continue to have great influence. The US Congress had released a flood of funding for Alzheimer’s research, US$2.6 billion for last year’s budget, far outstripping that for the rest of the NIA, and Masliah was an ideal choice for its neuroscience division director. This was a position which was enormously influential for Alzheimer’s research in the US as well as internationally, allowing him to fund selected research over and above others with better scores form peer-review.

One of the drugs being developed based on his work is prasinezumab, which failed to show benefit over placebo in a trial of 316 Parkinson’s patients – but resulting in a host of adverse effects, though none serious. The drug was based on an idea by Masliah and another scientist (whose papers were also seemingly doctored) that a vaccine-like approach could cause the body to create antibodies against harmful precursors in both Parkinson’s and Alzheimer’s.

Questions began to be raised about his research two years ago. These were assessed by a team of forensic analysts and a neuroscientist, who concluded, “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work.” They acknowledge that accidental duplication is a possibility, and that images can acquire artefacts resembling improper manipulation during the publication process.

Columbia University neurobiologist Mu Yang used specialised software to detect similarities and alterations in images. She had previously worked with the team investigating manipulation in Alzheimer’s and stroke data. In her analysis, duplicated sections in certain Western blots that had been “seamlessly blended” quickly floated into view, she said. “It tells me someone put a lot of thought and effort into the image … and usually indicates something is very wrong.”

A team of 11 neuroscientists was less charitable when they viewed the images. Samuel Gandy, a prominent neurologist at the Mount Sinai Alzheimer’s Disease Research Center said that he was “floored” by what he saw, noting that even a “bus driver” could see that two images of a mitochondrion published two years apart were identical. “Hundreds of images,” he said in a video interview. “There had to have been ongoing manipulation for years.”

In response to this latest dossier, the NIH issued a statement stating that there was a finding of “research misconduct” for Masliah over reuse of figures in two papers, further stating that Masliah no longer serves as NIA’s neuroscience division director. The NIH stated that it had started its own investigation in 2023.

Source: Science

Categories : Neurodegenerative DiseasesTags :

Why do Some Parkinson’s Disease Treatments Affect Decision Making?

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Parkinson’s disease, a debilitating nervous system disorder, is treated with medications that sometimes cause impaired decision-making and poor impulse control. Now, researchers from Fujita Health University in Japan have identified a structure in the brain called the external globus pallidus which may be responsible for this side effect, paving the way for new treatments.

Parkinson’s disease (PD), also known simply as Parkinson’s, is a disorder of the nervous system that affects millions of people worldwide. The nerve cell damage associated with Parkinson’s can cause tremors, slowed movements, problems with balance, and many other symptoms which worsen gradually over time. Although there is no cure, there are medications available that can treat PD symptoms. Some of these medications, however, have previously unexplained side effects – including impaired decision-making that leads to potentially harmful behaviours such as pathological gambling, binge eating and compulsive shopping.

Now, in a study published in the International Journal of Molecular Sciences, researchers at Fujita Health University in Japan, led by Assistant Professor Hisayoshi Kubota from the Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, have investigated the mechanism by which a drug called pramipexole or PPX impairs the decision-making process in mice with Parkinson’s disease. The research was co-authored by Professor Taku Nagai from the Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), and Professor Hirohisa Watanabe from the Department of Neurology, School of Medicine, both at Fujita Health University.

To take a closer look at the findings of this study, we first need to understand how PPX works to alleviate PD symptoms. PD mainly results from a loss of nerve cells or neurons that produce a compound called dopamine. Some neurons are dependent on dopamine for their regular functioning – they have structures called ‘dopamine receptors’ which can be thought of as locks which can then be activated using dopamine as the ‘key’. Drugs like PPX can imitate the function of dopamine and bind to these receptors instead, especially in patients with PD who lack dopamine-producing neurons.

To study the effects of PPX on PD, the researchers injected the brains of mice with a toxin called 6-hydroxydopamine (or 6-OHDA). 6-OHDA damages neurons in a very similar manner to that observed in the brains of patients with PD. The mice were treated with PPX and then subjected to a touchscreen-based ‘gambling task’ to test their decision-making skills. Interestingly, these mice picked the high-risk/high-reward option much more often – they opted for a disadvantageous outcome where they received a large reward (of strawberry milkshake), which also comes with an increased risk of a large punishment by exposure to flashing lights.

But which part of the brain is responsible for this behaviour? Investigating the brains of mice treated with PPX revealed that a region deep inside the brain called the external globus pallidus (GPe) was hyperactivated, or showed a much higher level of neuron activity. The researchers then chemically inhibited the neurons in the GPe, which actually reduced disadvantageous risk-taking activity in the mice. This proved that hyperactivation of the GPe was indeed responsible for poor decision-making in the mice treated with PPX.

This study has huge implications for treating patients with Parkinson’s disease. “Our findings could lead to the development of new medications or interventions that specifically target the external globus pallidus,” explains Dr. Kubota. “This would help to prevent or reduce decision-making impairments in Parkinson’s disease patients.“

Besides helping medical professionals develop better treatments for Parkinson’s disease, these findings can also help improve awareness among affected patients, their families, as well as the general public. Dr. Kubota, explains that “Investigating how Parkinson’s disease medications affect decision-making will help the public to better understand the complexity of the disease and its treatment.” He also says “This will benefit patients, their families and carers, and motivate them to consider early care and preventive strategies.”

These findings shed new light on the complex processes in the brain that aid our everyday decision-making skills, and promise to improve quality of life for patients affected by Parkinson’s disease. Maybe we can take away some important lessons from this study as well, and think twice before we indulge in poor decision-making in our daily lives!

Categories : Neurodegenerative DiseasesTags :

SGLT-2 Inhibitors may Lower Risk of Dementia and Parkinson’s Disease

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A class of drugs for diabetes may be associated with a lower risk of dementia and Parkinson’s disease, according to a study published in Neurology®, the medical journal of the American Academy of Neurology. The study looked at sodium-glucose cotransporter-2 (SGLT2) inhibitors, which are also known as gliflozins. They lower blood sugar by causing the kidneys to remove sugar from the body through urine.

“We know that these neurodegenerative diseases like dementia and Parkinson’s disease are common and the number of cases is growing as the population ages, and people with diabetes are at increased risk of cognitive impairment, so it’s encouraging to see that this class of drugs may provide some protection against dementia and Parkinson’s disease,” said study author Minyoung Lee, MD, PhD, of Yonsei University College of Medicine in Seoul, South Korea.

The retrospective study looked at people with type 2 diabetes who started diabetes medication from 2014 to 2019 in South Korea. People taking SGLT2 inhibitors were matched with people taking other oral diabetes drugs, so the two groups had people with similar ages, other health conditions and complications from diabetes.

Then researchers followed the participants to see whether they developed dementia or Parkinson’s disease. Those taking the SGLT2 inhibitors were followed for an average of two years and those taking the other drugs were followed for an average of four years.

Among the 358 862 participants with an average age of 58, a total of 6837 people developed dementia or Parkinson’s disease during the study. For Alzheimer’s disease, the incidence rate for people taking SGLT2 inhibitors was 39.7 cases per 10 000 person-years, compared to 63.7 cases for those taking other diabetes drugs. Person-years represent both the number of people in the study and the amount of time each person spends in the study.

For vascular dementia, which is dementia caused by vascular disease, the incidence rate for people taking the SGLT2 drugs was 10.6 cases per 10 000, compared to 18.7 for those taking the other drugs. For Parkinson’s disease, the incidence rate for those taking the SGLT2 drugs was 9.3 cases per 10 000, compared to 13.7 for those taking the other drugs.

After researchers adjusted for other factors that could affect the risk of dementia or Parkinson’s disease, such as complications from diabetes and medications, they found that SGLT2 inhibitor use was associated with a 20% reduced risk of Alzheimer’s disease and a 20% reduced risk of Parkinson’s disease. Those taking the drugs had a 30% reduced risk of developing vascular dementia.

“The results are generally consistent even after adjusting for factors like blood pressure, glucose, cholesterol and kidney function,” Lee said. “More research is needed to validate the long-term validity of these findings.” Lee said that since participants were followed for less than five years at the most, it’s possible that some participants would later develop dementia or Parkinson’s disease.

Source: American Academy of Neurology