Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies.

α-synucleinopathies are progressive neurodegenerative disorders characterized by intracellular aggregation of α-synuclein, yet their molecular pathogenesis remains unknow. Here, we explore cell-specific changes in gene expression across different α-synucleinopathies. We perform single-nucleus RNA sequencing on nearly 300,000 nuclei from the prefrontal cortex of individuals with idiopathic Parkinson's disease (iPD, n = 20), Parkinson's disease caused by LRRK2 mutations (LRRK2-PD, n = 7), multiple system atrophy (MSA, n = 6) and healthy controls (n = 13).

Risk factors and evolution of weight loss in Parkinson's disease: A 9-year population-based study.

Introduction: Weight loss is considered a common complication of Parkinson's disease (PD), but there are few prospective longitudinal studies on weight loss in patients followed from time of PD diagnosis. We sought to determine the frequency, evolution and risk factors of weight loss in a representative incident PD cohort.

Methods: In this prospective population-based observational study, we followed 180 newly-diagnosed, initially drug-naïve PD patients and 161 controls with repetitive weight examinations over 9 years.

Amyotrophic lateral sclerosis caused by the expansion in Norway - prevalence, ancestry, clinical characteristics and sociodemographic status.

Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a expansion (C9).

Brain Proteome Profiling Reveals Common and Divergent Signatures in Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

The molecular pathogenesis of degenerative parkinsonisms, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and Multiple system atrophy (MSA), remains largely unknown. To gain novel insight into molecular processes associated with these diseases, we conducted a proteome-wide expression study in prefrontal cortex tissue from a cohort of 181 individuals, comprising PD (N = 73), PSP (N = 18), MSA (N = 17) and healthy control (N = 73). Using marker gene profiles, we first assess the cellular composition of the samples and, subsequently, identify distinct protein signatures for each disease, while correcting for cell composition.

Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson's Disease.

Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson's disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years.