Publications by authors named "Wolfgang Oertel"

Article Synopsis
  • The study investigates how pathological aggregation of α-synuclein (aSYN) contributes to neuron dysfunction in Parkinson's disease, focusing on mitochondrial impact.
  • Researchers injected pre-formed aSYN fibrils into specific mouse brain regions and employed various techniques to analyze the effects 12 weeks later.
  • Results showed that aSYN accumulation led to neuronal loss, reduced mitochondrial function, increased oxidative stress, and compromised energy production in dopaminergic neurons, suggesting mitochondrial disruption as an early event in the disease process.
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Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson's disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic "Parkinson-Disease-related-Pattern (PDRP)"-z-score in F-fluorodeoxyglucose positron emission tomography (FDG-PET).

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Article Synopsis
  • Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease linked to abnormal tau protein accumulation, and previous studies were limited in exploring rare genetic variants due to the use of genotype arrays.* -
  • In this study, whole genome sequencing (WGS) on a large cohort allowed researchers to confirm known genetic loci related to PSP and discover new associations, particularly highlighting a different role for the APOE ε2 allele compared to Alzheimer's disease.* -
  • The findings expand knowledge of PSP's genetic underpinnings and identify potential targets for future research into the disease's mechanisms and treatments.*
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Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson's Disease (PD) are in early phases of clinical testing. Involving patients' preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects.

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Article Synopsis
  • Researchers aim to create a new assay using surface plasmon resonance (SPR) to identify compounds that can detect fibrillar forms of alpha-synuclein and 4-repeat tau, which are important in neurodegenerative diseases.
  • They optimized the SPR protocol to analyze the binding properties of various fluorescent ligands with different fibrils, identifying multiple binding sites on the fibrils and validating findings through immunofluorescence in brain tissue samples.
  • The study suggests that this SPR approach could effectively characterize small molecules for targeting proteinopathies associated with neurodegenerative diseases, improving our understanding of these conditions.
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The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption.

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Article Synopsis
  • Restless legs syndrome (RLS) affects nearly 10% of older adults, but many face delays in diagnosis and treatment.
  • A large-scale genetic study identified 164 risk loci for RLS, enhancing our understanding of its genetic basis and showing similarities in genetic predispositions between sexes.
  • Findings suggest potential drug targets, a relationship between RLS and diabetes, and highlight the effectiveness of machine learning in predicting RLS risk using genetic and other data.
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Background: Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alpha-synucleinopathies such as Parkinson's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed in PD. However, relatively little is known about whole-brain functional brain alterations in iRBD.

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Importance: The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H1 and H2, various structural forms of 17q21.

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One of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely.

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BACKGROUND: Epidemiologic studies show that smokers have a lower incidence of Parkinson’s disease. Nicotine has been hypothesized to slow progression in early Parkinson’s disease. METHODS: In a double-blind, placebo-controlled multicenter trial, we randomly assigned patients with Parkinson’s disease, diagnosed within 18 months, who were in Hoehn and Yahr disease stage less than or equal to 2 (range from 0 to 5; higher scores indicate greater impairment), who were therapy naïve (except for stable monoamine-oxidase-B inhibition), and not requiring dopaminergic therapy, to transdermal nicotine or placebo.

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Article Synopsis
  • Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease linked to tau protein accumulation, and previous studies using genotype arrays overlooked important genetic variations like rare variants and structural changes.* -
  • This study utilized whole genome sequencing (WGS) involving 1,718 PSP patients and 2,944 controls, confirming known genetic markers and discovering new associations, including the unique role of the ε2 allele as a risk factor.* -
  • The findings from this research advance the understanding of PSP genetics, highlighting potential new targets for disease mechanisms and treatment strategies.*
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Background: Pathological accumulation of aggregated α-synuclein (aSYN) is a common feature of Parkinson's disease (PD). However, the mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. A potentially relevant target of aSYN is the mitochondrion.

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Importance: Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.

Objective: To investigate whether α-synuclein in neuronally derived serum-extracellular vesicles identifies individuals at risk of developing PD and related dementia.

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Article Synopsis
  • - This study examined how speech and language impairments relate to outcomes in patients with isolated REM sleep behavior disorder (iRBD) across seven different language-speaking centers.
  • - Researchers used advanced speech analysis techniques to identify distinct patterns of language deterioration and followed 180 patients over about 2.7 years, discovering that 26.9% developed neurodegenerative diseases.
  • - Results indicated that greater severity in linguistic and acoustic abnormalities significantly predicted the likelihood of developing conditions like dementia or parkinsonism, suggesting automated language analysis can be a useful predictive tool for identifying patients at risk.
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Background: Reduced gastric motility in Parkinson's disease (PD) has been reported, but hardly any study exists in subjects with isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD), a specific prodrome of α-synucleinopathies.

Objectives: We compared the gastric motility of 17 iRBD subjects with that of 18 PD subjects (15 drug naive, 3 early treated in defined off) and 15 healthy controls (HC) with real-time magnetic resonance imaging (rtMRI).

Methods: After overnight fasting, participants consumed a standardized breakfast and underwent a 3-T rtMRI of the stomach.

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Mitochondrial dysfunction is strongly implicated in the etiology of idiopathic and genetic Parkinson's disease (PD). However, strategies aimed at ameliorating mitochondrial dysfunction, including antioxidants, antidiabetic drugs, and iron chelators, have failed in disease-modification clinical trials. In this review, we summarize the cellular determinants of mitochondrial dysfunction, including impairment of electron transport chain complex 1, increased oxidative stress, disturbed mitochondrial quality control mechanisms, and cellular bioenergetic deficiency.

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Article Synopsis
  • - Multiple system atrophy (MSA) is a severe disease with varying motor and autonomic symptoms, and previous studies have linked certain clinical factors to reduced survival rates.
  • - Researchers analyzed 210 MSA patients over 17 years to create a survival risk model using clinical factors like age at symptom onset and early autonomic failure.
  • - They developed a nomogram to predict individual survival probabilities over 7 years, which showed good accuracy and could enhance patient counseling and treatment strategies.
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One in eight individuals worldwide lives with a mental health disorder. For many European countries, the prevalence is even higher, with one in four people reporting mental health problems [1]. Three-quarters of all mental health disorders develop before age 25, with many presenting initially in undiagnosed forms already in the mid-teens and eventually manifesting as severe disorders and lasting into old age [2].

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Article Synopsis
  • A study investigated the relationship between the human leukocyte antigen (HLA) locus and synucleinopathies, specifically Lewy body dementia (LBD) and isolated REM sleep behavior disorder (iRBD), which are linked to neuroinflammation.
  • It was found that the HLA-DRB1*11:01 allele was significantly associated with iRBD, while several other alleles showed varying associations.
  • The results imply that the HLA locus may have distinct roles depending on the type of synucleinopathy being examined.
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Purpose: Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with F-FDG PET in iRBD is promising, but longitudinal studies are scarce.

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Background: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) cohorts have provided insights into the earliest neurodegenerative processes in α-synucleinopathies. Even though polysomnography (PSG) remains the gold standard for diagnosis, an accurate questionnaire-based algorithm to identify eligible subjects could facilitate efficient recruitment in research.

Objective: This study aimed to optimize the identification of subjects with iRBD from the general population.

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NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results.

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The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points.

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