Occupational histories in neuropathologically confirmed multiple system atrophy.

Purpose: This study examined occupational histories in multiple system atrophy to identify environmental associations of potential relevance to disease causation.

Methods: A total of 270 neuropathologically confirmed cases of multiple system atrophy obtained from the Mayo Clinic Brain Bank for neurodegenerative disorders in Jacksonville, Florida, were included in this case-control study. Demographic and disease information was collected from medical records.

Widespread Distribution of α-Synuclein Oligomers in -related Parkinson's Disease.

Mutations in leucine-rich repeat kinase 2 () are the most common cause of familial and sporadic Parkinson's disease (PD). While the clinical features of -PD patients resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of -PD cases do not have Lewy-related pathology.

Enhancing the Graduate Nursing Student Experience Through Gamification.

Gamification, the use of game-styled learning methods in non-game contexts, encourages student participation, increases learning motivation, and maximizes the amount of information students can retain. An intervention was designed utilizing gamification principles to reinforce material learned during a week-long regional anesthesia intensive. Students participated in team-based competitions consisting of knowledge-based questions, critical thinking, and hands-on ultrasound skills.

Taxonomic intestinal microbiota differences in Lewy body spectrum disease and cohabitant controls.

Background: Microbial dysbiosis has been reported to contribute to development of neurodegenerative diseases, however, there is a need to identify causative/prognostic indicators.

Objectives: To comparatively analyze gut microbiome composition in symptomatic LBD (dementia/mild cognitive impairment), iRBD, and cohabiting controls without LBD or iRBD.

Methods: 16S rRNA amplicon sequencing was performed in 38 cases (27 LBD, 11 iRBD) and 39 cohabitant controls.

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

Modeling Lewy body disease with triplication iPSC-derived cortical organoids and identifying therapeutic drugs.

Aggregated α-synuclein (α-SYN) proteins, encoded by the gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs)-derived cortical organoids generated from patients with LBD with gene triplication.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.

Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.

Associations of mitochondrial genomic variation with successful neurological aging.

Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.

Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.

Unmet Need in Early-Onset Parkinson's Disease: Deep Brain Stimulation and Pregnancy.

Pregnancy in women with early-onset Parkinson's disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

Distinct transcriptional alterations distinguish Lewy body disease from Alzheimer's disease.

Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by α-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, AD is characterized by amyloid plaques and neurofibrillary tangles.

Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease.

Despite substantial progress, causal variants are identified only for a minority of familial Parkinson's disease (PD) cases, leaving high-risk pathogenic variants unidentified. To identify such variants, we uniformly processed exome sequencing data of 2,184 index familial PD cases and 69,775 controls. Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.

Changes in plasma concentrations of novel vascular and inflammatory biomarkers in obstructive sleep apnea patients pre- and post-stroke.

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke.

Methods: In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression.

Results: Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs).

Human plasma-like medium (HPLM) induces cell morphologies.

The fungal pathogen ) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory conditions. Here, we describe cell morphologies when is grown in human plasma-like medium at 37°C, 5% CO.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.

Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.

Design, Setting, And Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020.