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While clinical literature shows correlations of biomarker levels in blood to disease symptom severity, disease specificity will likely require more than one single biomarker to tell the tale; a subject recently debated at the recent World Parkinson's Congress in Phoenix. What is even more relevant is whether a biomarker profile in the blood product (serum/plasma) correlates to the actual changes in neuron number or neuronal function in the disease-prone areas of the brain. Our newly posted preprint in bioRxiv addresses this question head-on. Using two established rat models of Parkinson's disease, we found that the levels of GFAP, UCHL-1, and NfL increase in the substantia nigra, in latter stages of tyrosine hydroxylase and dopamine tissue loss in both models. Crtically, these increases were associated with increased levels of all 3 in the serum in both models, indicating that the rise in blood levels was associated with changes in expression in a disease-prone area of the brain affected by Parkinson's disease.
In a collaborative study between the labs of Michael Salvatore and Chris Bishop (Binghamton University), we found that during the loss of nigrostriatal dopamine neurons in an established rat PD model, dopamine levels are unchanged despite 50% loss of neurons and the enzyme responsible for making dopamine in the substantia nigra. Two key elements from this major finding, published in the Int Journal of Molecular Sciences, are that this plasticity did not take place in the area of the brain far more commonly studies in models and patients alike (the striatum). Moreover, evidence for increased dopamine release was also found in the substantia nigra, but not the striatum. We believe this mechanism may be responsible for maintaining the ability to move during the prodromal (premotor impairment) phase of the disease, and as such, reveals a target by which to maintain movement as disease progression continues.
Combining an eye-tracking decision-making task with standard motor and cognitive tests may help detect Parkinson’s disease earlier, even before major movement symptoms appear.
Aerobic exercise can improve movement in Parkinson’s disease even after major dopamine loss, potentially reflected in reduced blood biomarkers of disease severity.
A human-like maze test in PINK1−/− rats may help detect early cognitive decline in Parkinson’s disease before motor symptoms appear.
In a Parkinson’s rat model, early dopamine boosts may delay movement problems, but aging reduces this compensation, leading to motor decline.
Parkinson’s research may be missing half the picture—dopamine changes in a second brain area, the substantia nigra, could be just as important for movement as the well-studied striatum.
In Parkinson’s, the brain boosts certain dopamine signals in one area to help delay movement problems, even as damage worsens.
GDNF therapy may fail if started late because key brain receptors decline, so boosting these receptors early might improve treatment in Parkinson’s.
Rodent models of Parkinson’s help us understand how exercise improves movement problems. But to apply this to people, we need to consider what patients are physically able to do.
Veterans with mild brain injuries have a higher risk of Parkinson’s, and spotting early thinking problems may help understand why.
Our latest publication in Frontiers in Psychiatry showcases how translational research connects preclinical discoveries to the Parkinson’s community—using the Iowa Gambling Task to illuminate subtle cognitive shifts across species.
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Scientists and Scholars
Sleep duration in middle-aged years of life predicts the age of diagnosis of Parkinson's disease Sleep Medicine: X, 8, 100123, doi: 10.1016/j.sleepx.2024.100123 Clark, C.E., Gold, J., & Rigby, B.R. (2024).
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Sleep duration in middle-aged adults is a key predictive variable on the age of diagnosis of Parkinson's disease.
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There is no interaction effect between sleep duration and physical activity on the age of diagnosis of Parkinson's disease.
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Moderate-intensity physical activity in middle-aged adults is a predicting variable on the age of diagnosis of PD.
Can exposure to heat attenuate neurodegeneration in older adults with Parkinson's disease? Clark, C.E. & Rigby, B.R. (2023). Frontiers in Aging Neuroscience, 15, 1239656. doi: 10.3389/fnagi.2023.1239656
In this opinion article, we suggest that heat exposure could be a low-cost, supplementary treatment for older adults with Parkinson’s disease. The basis of the argument is that raising core body temperature boosts heat shock proteins, which help prevent protein misfolding and aggregation that drive neurodegeneration. We caution that people with Parkinson’s often have impaired thermoregulation, thus core temperature should rise only 1–2°C and stay at or below 39°C. Because no direct trials exist yet, we recommended testing heat alone first, then heat combined with exercise.
The Essential Exercise Guide for Parkinson's Disease
This book written by Valerie Johnson, PT, DPT applies PD-specific, research-based exercise principles to help you maximize the
benefits of your exercise practice in order to drive back and stave off your PD symptoms. While
exercise also reduces non-motor symptoms of Parkinson's including anxiety, depression,
sleeplessness, fatigue and constipation, this book will focus on the improvements in motor
symptoms.
This new dopamine agonist, Tavapadon, targets the D1 dopamine receptor class. It is given once daily. Targeting the D1 class of receptors has a solid rationale to treating motor impairment in Parkinson's disease because its expression is not on the dopamine neurons themselves, but is on neurons that regulate basal ganglia output to promote movement initiation. Key points are that the part III UPDRS scores decreased in patients in this multi-center trial by ~9 points. At the end of the article, one can find information about current enrollment of de novo participants in an ongoing open-label extension trial (TEMPO-4 (NCT04760769).
Benefits of High vs Moderate Intensity Exercise
At the World Parkinson's Congress, there was considerable discussion about the benefits of exercise. The main symposium was extremely well-attended and we had the opportunity to sit at the Roundtable on Wednesday to discuss exercise impact. It is our opinion that, at this time, there is no consensus that high-intensity exercise provides a superior outcome to moderate intensity aerobic exercise. Evidence exists that regular practice of aerobic exercise at either intensity will provide a benefit in motor performance based upon the UPDRS part III scoring system. We believe the most important issues include compliance to an aerobic exercise regimen that is practicable for the patient's ability, and should be practiced ideally 3 times per week, for at least 30 min. Below, we provide links to the evidence that exists for exercise benefits practiced at either intensity. We include one paper from our group in this collection of reviews and primary research articles.
Most dopamine function in Parkinson’s disease is lost within the first few years after diagnosis—often before many neurons have fully died—suggesting the majority of degeneration occurs very early.
Avoiding medication timing issues, other complications while inpatient