Featured
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News & Views |
Disentangling clinical and biological trajectories of neurodegenerative diseases
In recent years, we have seen a shift towards defining sporadic neurodegenerative diseases as a biological continuum. Here, we discuss the risks associated with this shift, emphasize the importance of maintaining a strong connection between disease definitions and subsequent clinical outcomes, and suggest clinicobiological frameworks to disentangle multiple discrete nosological entities.
- Nicolas Villain
- & Vincent Planche
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Review Article |
Gaucher disease provides a unique window into Parkinson disease pathogenesis
The association between the rare, monogenic lysosomal storage disorder Gaucher disease and Parkinson disease has provided insights into the pathogenesis of this far more common neurodegenerative disease. Here, Sidransky and colleagues review the knowledge gained from decades of Gaucher disease research and explore the relationship between GBA1 and parkinsonism.
- Ellen Hertz
- , Yu Chen
- & Ellen Sidransky
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Comment |
Focused ultrasound brain therapy is a new tool in the box
Similar to any innovation that disrupts the status quo, the advent of magnetic resonance-guided focused ultrasound in neurology was accompanied by controversy and debate. However, evidence suggests that this therapeutic tool, which is already widely used to treat tremor and Parkinson disease, is gaining acceptance and will become a viable therapeutic option for various other neurological conditions in the near future.
- Raúl Martínez-Fernández
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News & Views |
Towards the era of biological biomarkers for Parkinson disease
Since its instigation in cancer research in the 1930s, the disease-staging concept has become a crucial tool in clinical research and medical practice. Two new papers have proposed biological staging and classification systems based on α-synuclein pathology for Parkinson disease and related conditions.
- Nobutaka Hattori
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Research Highlight |
Parkinson disease pathology in inflammatory bowel disease
A new study has found evidence of α-synuclein aggregates — a key pathological hallmark of Parkinson disease — in the gut and brain in people and animals with inflammatory bowel disease.
- Heather Wood
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Correspondence |
Reply to: Questioning the cycad theory of Kii ALS–PDC causation
- Katerina Menšíková
- , Raymond Rosales
- & Petr Kaňovský
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Review Article |
Parkinson disease psychosis: from phenomenology to neurobiological mechanisms
Parkinson disease psychosis comprises a spectrum of illusions, hallucinations and delusions that emerge during the disease course. This Review considers clinical, neuroimaging and neurochemical evidence that might aid early identification of psychotic phenomena in people with Parkinson disease and inform new therapeutic strategies.
- Javier Pagonabarraga
- , Helena Bejr-Kasem
- & Jaime Kulisevsky
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Perspective |
Next-generation sequencing and bioinformatics in rare movement disorders
In this Perspective, Zech and Winkelmann outline multidimensional strategies for genetic diagnosis in patients with rare movement disorders and highlight community-driven data-sharing and case-matchmaking platforms designed to foster the discovery of new genotype–phenotype relationships.
- Michael Zech
- & Juliane Winkelmann
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Comment |
Glyphosate and neurotoxicity — a call for scientific renewal
Glyphosate, a controversial herbicide, has been approved for use in the European Union for another 10 years despite uncertainty over whether it increases the risk of neurodegenerative disorders such as Parkinson disease. We call for new approaches to assessing the neurotoxicity of glyphosate and other pesticides and improving their regulation.
- Bastiaan R. Bloem
- , Tjitske A. Boonstra
- & Roel C. H. Vermeulen
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Perspective |
A multiple hits hypothesis for memory dysfunction in Parkinson disease
This Perspective proposes a tripartite model involving the amygdala, hippocampus and striatum as key structures underlying cognitive dysfunction in Parkinson disease. The authors explore the anatomical and functional relationships of the structures and summarize evidence of their involvement in the cognitive aspects of the disease.
- Salvatore Citro
- , Giulia Di Lazzaro
- & Paolo Calabresi
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Research Highlight |
CD11c+ macrophages mediate brain-to-gut α-synuclein trafficking
New research indicates that in a mouse model of Parkinson disease, α-synuclein is trafficked from the brain to the gut by CD11c-expressing macrophages.
- Heather Wood
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Research Highlight |
A new biological classification for Parkinson disease
In a plenary lecture at the XXVI World Congress of Neurology, Anthony Lang presented a new biological classification model for Parkinson disease.
- Heather Wood
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Research Highlight |
27-Hydroxycholesterol propagates α-synuclein pathology in Parkinson disease
New research in a mouse model of Parkinson disease indicates that the cholesterol metabolite 27-hydroxycholesterol drives α-synuclein pathology.
- Lisa Kiani
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Comment |
AI and deep brain stimulation: what have we learned?
Deep brain stimulation (DBS) is a well-established approach for treating movement disorders such as Parkinson disease, dystonia and essential tremor. However, the outcomes are variable, and researchers are now exploring artificial intelligence-based strategies to help improve DBS procedures.
- Patricia Limousin
- & Harith Akram
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Research Highlight |
Continuous levodopa production by an artificial enzyme
Researchers in China have developed a functional nucleic acid-based responsive artificial enzyme that enables continuous production of levodopa in a mouse model of Parkinson disease.
- Heather Wood
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Review Article |
The noradrenergic subtype of Parkinson disease: from animal models to clinical practice
Some patients with Parkinson disease (PD) present with mostly non-motor symptoms. Here, Chaudhuri et al. discuss the evidence for CNS abnormalities in noradrenergic function in these individuals. Recognition of this noradrenergic subtype of PD might ultimately lead to subtype-specific treatments and personalized medicine.
- K. Ray Chaudhuri
- , Valentina Leta
- & Per Svenningsson
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Research Highlight |
A seed amplification assay to detect Parkinson disease pathology
An α-synuclein seed amplification assay can reliably identify people with Parkinson disease, even at the prodromal stage, new research indicates.
- Heather Wood
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Research Highlight |
Gut microbiome changes linked to Parkinson disease
A new study used a metagenomic approach to survey the entire gut microbiome in people with Parkinson disease and identified specific changes that could be linked to the pathogenesis of the disease.
- Heather Wood
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Research Highlight |
Glial response to Parkinson disease-like neurodegeneration is region-dependent
According to new findings in a mouse model of Parkinson disease, the glial response to nigrostriatal degeneration differs depending on brain region.
- Sarah Lemprière
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News & Views |
First trials test targeting of α-synuclein for Parkinson disease
In the first two phase II trials of therapies that target α-synuclein to treat Parkinson disease, the primary endpoints were not met. However, the limitations of these studies need to be addressed in future trials and alternative approaches to targeting α-synuclein should be pursued before α-synuclein is discounted as a target.
- Lorraine V. Kalia
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Research Highlight |
Transmembrane protein interacts with α-synuclein to confer risk of PD
According to new findings, the transmembrane protein GPNMB is the mechanistic link between a Parkinson disease risk locus and α-synuclein pathology.
- Sarah Lemprière
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Review Article |
The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic
The prominence of gastrointestinal dysfunction among the non-motor features of Parkinson disease (PD) indicates a close bidirectional link between the brain and the gut. This Review discusses the proposed roles of gut-related factors in PD development, progression and treatment responses, and as therapeutic targets.
- Ai Huey Tan
- , Shen Yang Lim
- & Anthony E. Lang
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Perspective |
Closing the loop for patients with Parkinson disease: where are we?
In this Perspective, the authors present their vision for a closed-loop system for automatic symptom monitoring and levodopa administration in individuals with Parkinson disease. The system would capitalize on the ongoing advances in wearable sensor technology, drug delivery systems and machine learning.
- Hazhir Teymourian
- , Farshad Tehrani
- & Joseph Wang
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Review Article |
Multimodal brain and retinal imaging of dopaminergic degeneration in Parkinson disease
In vivo imaging biomarkers for early diagnosis and monitoring of Parkinson disease (PD) are important for the development of new therapies. The authors review recent advances in brain and retinal imaging in PD, focusing particularly on multimodal approaches with applications at the prodromal stage.
- Jee-Young Lee
- , Antonio Martin-Bastida
- & Beomseok Jeon
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Perspective |
Neurogenetic disorders across the lifespan: from aberrant development to degeneration
Traditionally, CNS diseases have been classified into early-onset neurodevelopmental disorders and late-onset neurodegenerative disorders. However, as this article highlights, we now recognize that developmental and neurodegenerative disorders can involve shared mechanisms, with some classic neurodegenerative diseases also having a neurodevelopmental component.
- Richard A. Hickman
- , Sarah A. O’Shea
- & Wendy K. Chung
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Research Highlight |
VEGFA mediates blood–brain barrier disruption in Parkinson disease
- Heather Wood
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Review Article |
Circadian rhythms in neurodegenerative disorders
In this Review, Nassan and Videnovic discuss the alterations to the circadian system that occur in neurodegenerative disorders and highlight future directions for research in the field, including opportunities for the development of circadian-based therapeutic interventions.
- Malik Nassan
- & Aleksandar Videnovic
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News & Views |
Digital assessment at home — mPower against Parkinson disease
Results of a new study have shown the enormous potential of smartphone-collected, real-world data for the differentiation of patients with Parkinson disease from controls. This study spearheads a new phase for the evaluation of symptoms associated with Parkinson disease that is patient-centred, digital, objective, continuous and relevant to everyday life.
- Walter Maetzler
- & Andrea Pilotto
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News & Views |
The Parkinson disease connectome — insights from new imaging studies
During Parkinson disease progression, the accumulation of α-synuclein pathology is paralleled by changes in structural and functional connectivity in the brain. Two new studies pinpoint specific alterations in the brain connectome in the early stages of Parkinson disease and suggest future avenues of research to develop connectome-based biomarkers.
- Florian Krismer
- & Klaus Seppi
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News & Views |
Parkinson disease and air pollution: does what we breathe matter?
Results of a new study have identified an association between risk of incident Parkinson disease and exposure to NO2, which is released into the atmosphere as a result of burning fuels. Parkinson disease has a long prodromal phase, so these findings suggest an opportunity to apply early prevention strategies.
- Lilian Calderón-Garcidueñas