Tangled Up with Dementia in Parkinson’s Disease


Sherri Journeying Through

A reader recently posed the following question: “Why are there never any comments on dementia in regards to Parkinson’s disease? It is very real, and 40 percent of Parkinson’s patients deal with it.”

So, I began looking into it. My answer could have been, “Because I don’t want to think about that stuff.”

The idea that this disease could dominate my mind (as opposed to taking over my “brain”), among the other things it’s already taken from me, is frightening. And it’s a real possibility.

It is estimated that 50 to 80 percent of people with Parkinson’s disease (PD) will develop dementia. It takes about 10 years from the onset of PD to develop dementia, according to the Alzheimer’s Association.

In those with PD dementia, “plaques” and “tangles” are present. Plaques (not the kind dentist removes from your teeth) are deposits of a type of protein that form around nerve cells. These little monsters begin to cling to one another and form clumps, plaques, which prevent nerve cells from sending messages to each other properly.

Tangles, not the kind you comb out of your hair, are formed of tau protein, found in nerve cells. They are either on their way or have made it to death row. They bunch together, twisting around each other and forming tangles of nerve cell fibers. While tangling up the parallel strands of tau protein nerve cells, they fall apart, disintegrate, and cripple the cells’ communication system.

While this is going on, unawares to the patient, the plaques and the tangles continue to gather inside of the brain, causing other nice and healthy nerve cells to eventually wither away and die a silent death, leading to shrinkage in the area of the brain in which these little monsters had their fun fest.

Plaques and tangles present further complications in people with Parkinson’s, as these are the hallmark brain changes linked to Alzheimer’s disease.

I warned you. I told you we didn’t want to think about this stuff. But, unfortunately, it’s a part of the reality of Parkinson’s disease we must be aware of, not so we can worry and fret, but so that we can receive treatment sooner rather than later.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

The post Tangled Up with Dementia in Parkinson’s Disease appeared first on Parkinson’s News Today.

Small Vessel Disease Linked to Severity of Motor Impairment in Parkinson’s Patients, Study Finds

small vessel disease

A disorder related to tiny blood vessels in the brain, known as cortical small vessel disease, is directly linked to worsening motor function in Parkinson’s disease, according to a recent study.

An additional association between modifiable vascular risk factors, in particular hypertension, and dementia highlights the need to manage these risk factors in Parkinson’s patients.

The study, “Impact of small vessel disease on severity of motor and cognitive impairment in Parkinson’s disease,” was published in the Journal of Clinical Neuroscience.

Symptoms of Parkinson’s disease can be affected by different risk factors — any attribute, characteristic, or exposure of an individual that increases the likelihood of developing a disorder or injury. Notably, issues with the heart and its blood vessels, or cardiovascular risk factors, have been shown to contribute to greater motor dysfunction in Parkinson’s disease.

In addition, disorders rooted in the brain’s blood vessels, or cerebrovascular pathologies, are linked with an increased prevalence of parkinsonian symptoms, such as motor dysfunction, and cognitive impairment in the elderly.

The relationship among cortical small vessel disease — an umbrella term covering a variety of abnormalities related to small blood vessels in the brain — cognitive decline, and dementia is well-established. Despite this, small vessel disease is not considered a significant cause underlying cognitive impairment in Parkinson’s, and it is not clear whether and to what extent its symptoms and progression contribute to Parkinson’s motor severity and cognitive impairment.

Some of the most concrete evidence for understanding the impact of comorbidities — the simultaneous presence of two chronic diseases or conditions in a patient — in Parkinson’s and other neurodegenerative diseases has been obtained through autopsies of patients’ brains.

By comparing the clinical information collected from patients, such as motor function and cognitive ability, during treatment with an autopsy report, doctors can better assess the link among risk factors, the course of Parkinson’s disease, and the severity of parkinsonian symptoms and dementia.

Cerebrovascular disease pathologies, such as small vessel disease, have only been assessed in a limited number of autopsy studies of Parkinson’s patients.

Now, researchers at the University of Sydney Medical School in Australia have studied the relationship among vascular risk factors and small vessel disease and the severity of motor impairment, cognitive dysfunction, and dementia in Parkinson’s patients. Vascular risk factors studied included stroke, heart disease, hypertension, diabetes, and cigarette smoking.

To do so, they examined clinical information from 77 autopsy-confirmed Parkinson’s patients who were similar in age, cause of death, and duration or severity of Parkinson’s disease.

The researchers then examined clinical information collected during patient visits to determine the severity of cognitive dysfunction and motor impairment. The severity of motor impairment and disease progression was determined using the Hoehn and Yahr scale, while the Clinical Dementia Rating was used to assess the severity of cognitive dysfunction and progression.

Of the 77 patients, 65 percent had advanced-stage dementia. The mean duration of Parkinson’s disease was 12 years for patients with and without dementia. Patients with dementia had more vascular risk factors than those without dementia, including stroke, heart disease, hypertension and diabetes, and a longer history of cigarette smoking.

Researchers observed that the severity of small vessel disease was related to the degree of motor impairment. They did not find a link between the severity of small vessel disease and the presence of dementia in these patients.

They also found a link between the severity of modifiable vascular risk factors and cognitive impairment in the autopsies of Parkinson’s patients. Among the vascular risk factors, only hypertension was linked with cognitive impairment and dementia.

“Modifiable vascular risk factors relate most to the severity of cognitive rather than motor impairment in Parkinson’s disease,” the researchers wrote. This emphasizes the importance “of a holistic approach to the treatment of PD  [Parkinson’s disease] including the potential for longterm cognitive benefits of early and aggressive management of vascular co-morbidities.”

“Our study suggests that neurologists treating patients with Parkinson’s disease should proactively manage their patient’s vascular risk factors, which may reduce gait and cognitive impairment, two of the main clinical features that undermine well-being and independence in patients with Parkinson’s disease,” lead study author Jillian Kril, PhD, said in a news article published in Neurology Today.

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First Patient Dosed with VY-AADC Gene Therapy in Parkinson’s Phase 2 Trial


Voyager Therapeutics has begun patient dosing in a Phase 2 trial testing its investigational VY-AADC gene therapy in Parkinson’s patients whose motor symptoms are not responding adequately to oral medication.

The trial, called RESTORE-1 (NCT03562494), is recruiting participants across seven sites in the United States.

VY-AADC is a therapy that delivers the DDC gene, which provides instructions for making the AADC enzyme, directly to brain cells in the putamen region. The enzyme converts the standard-of-care Parkinson’s treatment levodopa into dopamine, the signaling molecule that is lacking in Parkinson’s disease.

The approach is expected to bypass the effects of degenerating dopamine neurons in the substantia nigra, a part of the midbrain, by increasing dopamine levels in the putamen.

In an ongoing Phase 1b trial (NCT01973543), a single administration of the therapy induced robust and durable improvements in patients’ motor function up to three years after treatment.

The treatment also effectively increased AADC enzyme activity, allowing patients to reduce their doses of oral levodopa. Also, patients reported significant improvement in quality of life.

The newly begun Phase 2 trial aims to determine whether VY-AADC is better than a placebo at reducing motor fluctuations in Parkinson’s patients whose symptoms are not effectively controlled with levodopa or related treatments.

The trial is expected to enroll approximately 42 patients who have been diagnosed with Parkinson’s disease for at least four years and are not responding adequately to oral medications. To be eligible, participants must be experiencing at least three hours of OFF time during the day, as measured by a validated, self-reported patient diary.

Participants will be randomized to receive either a single infusion of VY-AADC or a placebo into the brain via surgery. They will be followed for 12 months to determine their changes in motor fluctuations, changes in the ability to perform daily activities, and quality of life.

During the new Phase 2 trial, researchers will also determine the efficacy of treatment delivery by assessing AADC enzyme levels and activity in the putamen through positron emission tomography (PET). Changes in patients’ daily doses of oral levodopa and related medications will also be evaluated.

More information about RESTORE-1, including recruitment details, can be found here.

“Patients with Parkinson’s disease need new therapeutic options, especially as the disease progresses and there is less AADC enzyme in parts of the brain where it is needed to convert levodopa to dopamine,” Mark Richardson, MD, PhD, associate professor, director of Epilepsy and Movement Disorders Surgery at the University of Pittsburgh Medical Center and principal investigator in the RESTORE-1 trial, said in a press release.

The U.S. Food and Drug Administration granted regenerative medicine advanced therapy (RMAT) designation to VY-AADC for therapy-resistant motor fluctuations in Parkinson’s patients.

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Gut Bacteria Composition Linked to Parkinson’s Disease Severity, Study Shows

gut bacteria composition

The composition of intestinal bacteria in patients with Parkinson’s disease is correlated with disease severity and a worse prognosis, a study has found.

The study, “Gut microbiota are related to Parkinson’s disease and clinical phenotype,” was published in Movement Disorders.

Parkinson’s disease is a chronic and progressive neurodegenerative disorder, caused by the gradual loss of dopamine-producing neurons in the substantia nigra, a region of the brain responsible for movement control. Although the condition is mostly associated with motor symptoms, such as tremors, body rigidity, and balance instability, patients may also experience a series of non-motor symptoms.

Gastrointestinal problems, in particular constipation, are some of the most common non-motor symptoms of Parkinson’s. They are estimated to affect up to 80 percent of all patients and can occur years before the onset of the first motor symptoms.

Previous studies have shown that gut bacteria involved in the regulation of intestinal transit interact with the nervous system, “influencing brain activity, behavior, as well as levels of neurotransmitter receptors and neurotrophic factors,” according to the study. However, the impact of intestinal bacteria in neurological disorders, such as Parkinson’s disease, had never been investigated.

“Based on the early gastrointestinal involvement in PD [Parkinson’s disease] and the vast potential of microbiome-host interactions, we … hypothesized that the fecal microbiome of PD patients differs from that of matched control subjects in terms of bacterial diversity,” the researchers wrote.

To test this hypothesis, the University of Helsinki researchers compared the composition of intestinal bacteria found in stool samples from 72 patients with Parkinson’s disease and 72 healthy controls by genetic sequencing.

Data from the observational study (NCT01536769) revealed that patients with Parkinson’s had a 77.6% reduction in the amount of bacteria belonging to the Prevotellaceae family compared with controls. This family of bacteria, which includes the Prevotella genus, is a group of nonharmful bacteria that live in the colon and help break down complex foods.

“Our findings indicate that the Prevotella associated gut microbiome enterotype [bacteria that live in the intestine] could be underrepresented among PD patients. Investigating whether high abundance of Prevotellaceae has protective effects against PD or whether low abundance is rather an indicator of disturbed mucosal barrier function will be important,” the investigators wrote.

Interestingly, the amount of bacteria from the Enterobacteriaceae family was much higher in patients with postural instability and gait difficulty than in those with tremor-dominant (TD) symptoms. This family of bacteria includes several pathogens, such as Escherichia coli, and other species of harmless bacteria.

“In comparison with TD patients, patients with a non-TD phenotype progress faster [and] have a worse prognosis. Our results suggest that this may be associated with higher abundance of Enterobacteriaceae in the fecal microbiome of non-TD patients,” the researchers wrote.

“Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker,” they added.

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2018 Season of Giving


PAA is blessed to have an active, passionate, and growing support network of board members, volunteers, donors, sponsors, and thought leaders. It is because of this generous support – by people just like you – that PAA continues to fulfill and grow the promise of its mission to improve the lives of Parkinson’s patients, caregivers, and loved ones throughout Alabama. We hope you’ll consider a donation to the Parkinson Association of Alabama as part of your holiday giving plans. Every donation matters and plays a role in delivering the PD research and care programs that benefit those affected by Parkinson’s throughout the State.

Click here to donate online or contact Mary T if you’d like to send the gift of a PAA donation to a friend or loved one. For gift donations, we can send the lucky recipient a beautiful card on your behalf to notify them of your gift.

IRL790 Is Safe, Reduces Levodopa-induced Dyskinesia in Parkinson’s, Phase 1b Trial Shows

IRL790 and Parkinson's

IRL790, Integrative Research Laboratories‘ investigational treatment for Parkinson’s disease patients, was safe and reduced levodopa-induced dyskinesia, a Phase 1b trial shows.

The results were published in the journal npj Parkinson’s Disease in the study, “Safety and tolerability of IRL790 in Parkinson’s disease with levodopa-induced dyskinesia—a phase 1b trial.”

Parkinson’s disease is a central nervous system disorder characterized by low levels of dopamine, causing tremors, stiffness, or slowing of movement.

Levodopa, a medication that helps counteract the shortage of dopamine in the brain, is the gold standard for treatment of Parkinson’s patients. But more than half the patients who use levodopa experience abnormal, involuntary movements — dyskinesia — within the first five years of treatment.

Studies have shown that long-term treatment with levopoda increases levels of a dopamine receptor, called dopamine D3 receptor, that seems to correlate with levodopa-induced dyskinesia.

IRL790 is a central nervous system medication that mainly targets the dopamine D3 receptor. In rat models of Parkinson’s disease, the treatment reduced involuntary movements caused by levodopa treatment without compromising the animals’ locomotion. Also, IRL790 showed anti-psychotic properties, suggesting its potential for treating both dyskinesia and psychosis in Parkinson’s patients.

In a prior Phase 1 trial, researchers tested ascending doses of IRL790 in healthy male volunteers. The treatment had a very good safety profile, with no serious adverse events reported, even at doses higher than those planned for patients.

Now, a team at the Karolinska Institutet in Sweden conducted a Phase 1b trial to determine the treatment’s safety and efficacy in Parkinson’s patients experiencing levodopa-induced dyskinesia.

The study (NCT03531060) included 15 Parkinson’s patients (nine men and six women) who randomly received oral capsules of IRL790 (11 patients) or an oral placebo (four patients) for four weeks. During the trial, all patients continued receiving their regular medication.

The study’s main objective was to assess the treatment’s safety — measured through the number of adverse events, physical examination, electrocardiogram, heart rate, blood pressure, and other laboratory measurements — after four weeks.

Secondary measures included changes from baseline in dyskinesia, measured with the Unified Dyskinesia Rating Scale (UDysRS), and Parkinson’s scores, measured with the Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Kinetigraph.

Thirteen patients completed the 4-week study, with IRL790 given at an average daily dose of 18 mg.

Overall, 14 patients (93.3%) reported 62 adverse effects. Most were reported during the first two weeks — when the dose of IRL790 was adjusted to each patient — and were mild to moderate, easily mitigated by dose adjustments. No serious adverse effects were reported in any of the groups.

Patients taking IRL790 had a mean reduction of 8.2 percent in dyskinesia scores compared to those taking a placebo.

“Among patients treated with IRL790, 55.5% were assessed as having an improved global clinical condition, as compared with baseline (much improved/minimally improved),” researchers stated.

There were no changes in symptoms relating to parkinsonism, either in the UPDRS or in measurements from the Parkinson’s Kinetigraph, a wrist-worn device that evaluates bradykinesia (slowness of movement) and dyskinesia during activities of daily living.

The results show that “IRL790 can be safely administered to patients with advanced PD,  which will now “be of guidance for the design of phase 2 studies,” researchers said.

IRL790 is already being tested in a Phase 2 trial (NCT03368170), which will assess whether the treatment can reduce dyskinesia in a larger population (74 patients). The trial will also help establish the optimal dose for further testing.

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Enduring Through Parkinson’s Disease


Sherri Journeying Through

Someone once said, “Life is hard.”

Someone else said, “Life is hard, and then you die.”

Another said, “Life is hard, but God is good.”

That’s what I’m holding on to — the belief that although life is indeed hard, God is so very good. 

You awake refreshed to the sun on your face through the bedroom window. Outside, a nest of newly hatched finches wait for their morning feed. The moment you step out of bed, the hard part begins. The part where you remember that the car died last night; where you get to work early only to find out you’ve been laid off; where you receive a phone call filled with disturbing or life-altering news.

You step out of bed to conquer the first hurdle of the day, then face another day of hurdle-hopping gone awry. The frustration, grief, disappointment, and despair ooze into the tiny crevices of your heart and permeate your spirit.

Sound fateful? Fateful and familiar and — dare we admit it – even hopeless? Hopeless as though you will never crawl out of the hole you’re in. A very dark place strewn with heartache, hurt, loneliness, and grief. Unexpected tragedies and unfulfilled expectations. It can appear as if our lives are desecrated by these negative feelings, and sometimes they don’t just seem to be – they are.

While we experience heartache and grief as we journey through death and disease, we are reassured that we don’t travel alone. While we walk uneven roads and pass through deep, dark valleys as we run the race set before us, we need to remember this: We have a God who will never leave us, forsake us, or forget us.

Life is hard, but as one of my favorite Christmas cards reads, “The best days are yet to come.” Days filled with unquenchable joy. We thought we couldn’t endure a life with Parkinson’s disease, but we are enduring because He is journeying with us. Never leaving us, never forsaking us, never forgetting us, always with us. Just as He promised.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Older IBD Patients Show Increased Risk for Parkinson’s Disease, Study Suggests

IBD risk factor

Older patients with inflammatory bowel disease (IBD) are more likely to develop Parkinson’s disease than those without the condition, a meta-analysis suggests.

Whether the same association exists for younger patients — ages 59 or younger — remains to be determined, according to the researchers.

The study, “Older patients with IBD might have higher risk of Parkinson’s disease,” was published in the journal Gut.

The chronic activation of pro-inflammatory mechanisms, which occurs in autoimmune conditions, has been increasingly recognized as a critical contributor of neurodegenerative disorders.

Studies suggest that this may happen due to the “gut-brain axis” — the two-way communication between the nervous system and the intestine that monitors gut function and links certain regions of the brain to intestinal functions, such as immune activation or intestinal permeability.

In line with the findings, some studies have already reported that patients with IBD — an autoimmune condition characterized by chronic inflammation of the gut — are 22-41% more likely to develop Parkinson’s than those without IBD.

However, a case-control study that examined Medicare data from 89,790 Parkinson’s cases and 118,095 population-based controls suggested that IBD actually reduced the risk for Parkinson’s by 15%.

To clarify this association, a team at Sichuan University in China reviewed all studies investigating the link between IBD and risk of Parkinson’s. Five studies met the inclusion criteria defined by the team, including a total of 9,174,766 participants.

Overall, IBD patients did not have a significantly higher risk of Parkinson’s than reference individuals, nor did patients with ulcerative colitis or Crohn’s disease — the two main forms of IBD — when examined individually.

However, patients 60 years or older were found to have a 32% higher risk of developing Parkinson’s. Patients 50 years or younger did not show this association, the researchers said.

“Our meta-analysis showed that patients with IBD did not have an increased risk of PD; however, subgroup analysis with cohort studies showed that they might be associated with increased risk of PD,” the researchers wrote.

“Age has been regarded as an important risk factor for Parkinson’s disease,” they added, but the findings suggest that “age at IBD diagnosis might be a risk factor of Parkinson’s disease.”

Interestingly, the team found that some studies reported medication-related side effects in the IBD population that resembled parkinsonism in the older population.

“It is necessary to take it into consideration whether older people will take more medications, and whether these medications lead to a higher risk of Parkinson’s also needs further studies to verify in the future,” they said.

Additional well-designed observational studies are still warranted to further explore the risk of Parkinson’s disease within the younger IBD population, the team noted.

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Foot Problems as an Early Sign of PD: Oh, What a Drag It Is!

foot drag

Search on the internet for early signs of Parkinson’s disease. Surprisingly, you will not find foot drag on most of the lists. Yet, Ali Samil, in the chapter “Cardinal Features of Early Parkinson’s Disease,” in the book “Parkinson’s Disease: Diagnosis and Clinical Management,” lists foot drag as an important early symptom.

I have been dealing with foot drag for a few years — that squeak of the sneaker on the kitchen floor when the foot drag catches, scuff marks left behind. While at a professional conference, the foot drag caught the top edge of a stair just as I was headed down, and down I went, grasping the handrail to rescue an awful fall. Recently, it has been much worse, and oh, what a drag it is now.

Reflecting on it, it seems almost impossible that I could seriously hurt my foot walking on a flat, carpeted surface with no obstacles in the way. But that is exactly what happened. Walking barefoot on a carpeted floor, my foot dragged, and then my big toe jammed into the carpet — HARD! I screamed, tears flowed, and I fell to the floor weeping from the pain. The toe turned a nice purple shortly thereafter, but luckily nothing was broken. I don’t walk barefoot anywhere now, except for a few steps in and out of the shower.

I am surprised that there is not more mention of foot drag in the lists of early PD symptoms. If it is a cardinal early symptom, then both patients and care providers should be given the heads up (or maybe feet down), along with some guidelines on how to adjust.

If a patient does have this symptom, then perhaps it doesn’t show up all the time, but rather only during off periods and deep fatigue. If the patient has a favorite pair of shoes, then perhaps signs of the foot drag can be seen on the wear pattern in the shoes.

The indications of foot drag problems don’t have to be as dramatic as my story before they become something that needs attention. My attention is given to the footwear I purchase, limiting my walking during deep fatigue, and carefully watching my feet when changing surface levels (such as a curb on sidewalks).

Maybe there are readers out there who have dealt with foot drag and have a story to tell with suggestions about how to cope. Next time someone says to you, “Quit dragging your feet on this,” tell them about this column.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

The post Foot Problems as an Early Sign of PD: Oh, What a Drag It Is! appeared first on Parkinson’s News Today.

Low Doses of Herbicide and Lectins Led to Parkinsonism in Animals, Study Reports

pesticides and herbicides

Ingesting a once widely used herbicide called paraquat along with lectins — proteins in common foods that bind carbohydrates (e.g., sugars) — can lead to symptoms typical of Parkinson’s disease and known as parkinsonism, a study reported.

Importantly, this animal research provides a new preclinical model for testing treatments in forms of Parkinson’s disease influenced by environmental factors.

The study, “Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat,” was published in the journal Parkinson’s Disease.

Parkinson’s development in people has been linked to both genetic and environmental factors. Researchers need to model how these factors cause the disease to discover treatments for patients with different types of Parkinson’s.

Previous studies have modeled how high levels of individual neurotoxins and external factors such as diet are linked to Parkinson’s. But individuals, over the course of a lifetime, are more likely to be repeatedly exposed to low doses of toxins, or a combination of toxins, whose disease-causing capacity may be enhanced by factors that include diet.

For example, paraquat — a neurotoxin and herbicide once in wide use and still in restricted use in the U.S. though banned in Europe — has been linked to Parkinson’s disease (ways it can be ingested include drinking water). But it has only been studied in isolation and at doses far beyond those commonly encountered. Similarly, lectins — sugar-binding proteins commonly found in legumes and grains — have been linked with rare forms of parkinsonism.

For these reasons, researchers at Penn State College of Medicine sought to understand and model how repeated exposures to low doses of toxins and external factors contribute to Parkinson’s development. They sought to demonstrate how exposure to common levels of paraquat and lectin can induce disease symptoms.

The researchers applied low-level doses of paraquat and lectins to rats daily for a week, and after a couple of weeks, checked for symptoms of parkinsonism. They tested the animals for motor function and for the production of a misfolded protein called alpha-synuclein that is linked with the development of Parkinson’s disease. They detected a decrease in motor function and in the number of dopaminergic neurons (those that produce the brain signaling chemical dopamine), the generation of misfolded alpha-synuclein, and other symptoms typical of parkinsonism.

To confirm that the symptoms spotted were related to parkinsonism, the researchers performed tests to see if known Parkinson’s treatments — levodopa — could reverse the observed symptoms.

“After observing that these animals did indeed show symptoms of Parkinsonism, we wanted to double check and make sure we weren’t looking at animals that had these symptoms for another reason,” Thyagarajan Subramanian, a study co-author and professor of neurology at Penn State College of Medicine, said in a press release. “We administered levodopa … [and] saw a return to almost normal types of motor responses, which was a clear indication that we were looking at some sort of Parkinsonism.”

Increasing evidence suggests that environmental neurotoxins or misfolded alpha-synuclein proteins are transported from the gut to the brain through the vagus nerve — the nerve that enables communication between the gut and the brain— this way damaging dopaminergic neurons in the substantia nigra, a major brain region affected in Parkinson’s disease.

“We were able to demonstrate that if you have oral paraquat exposure, even at very low levels, and you also consume lectins — perhaps in the form of uncooked vegetables, dairy or eggs — then it could potentially trigger the formation of this protein alpha-synuclein in the gut,” Subramanian said. “Once it’s formed, it can travel up the vagus nerve and to the part of the brain that triggers the onset of Parkinson’s disease.”

Interestingly, removing the vagus nerve before exposing the animals to paraquat and lectins protected them from parkinsonism.

The researchers plan to test whether medical treatments or dietary modifications can interfere with the transport of alpha-synuclein from the gut to the brain via the vagus nerve in this new model of Parkinson’s incorporating environmental factors.

They intend to test a substance called squalamine, which has been shown to remove alpha-synuclein from the gut and is now in clinical trials for treating Parkinson’s symptoms. 

“This study gives solid evidence that lectins, while in the presence of certain toxins, may be one potential culprit for the cause of Parkinsonism,” Subramanian said. “Additionally, this animal model can be a tool in the future to continue developing new medications and treatments for Parkinson’s disease.”

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