Lila Sciences

Genetically mediated increased expression of syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed risk mechanism for progressive supranuclear palsy and sporadic prion disease. Increased syntaxin-6 protein levels are also causally associated with Alzheimer's disease, suggesting it may have shared roles across multiple neurodegenerative diseases. However, no study has validated its functional role in tauopathies. To validate a role for syntaxin-6 in tauopathy pathogenesis, we knocked out syntaxin-6 in humanised P301S tauopathy mice. Mice underwent longitudinal rotarod testing, gait analysis, frailty and weight assessment, with neuropathological, biochemical and pathological analyses at 3 and 5 months. Stx6+/+;hTauP301S/P301S mice showed motor impairment from 1 month of age, which was partially rescued by syntaxin-6 knockout from months 1 to 4, with additional protection of gait at 5.5 months. Physiologically, syntaxin-6 knockout exerted a protective effect on weight trajectories and measures of frailty. Reduced neurodegeneration in the superficial cortex was observed at 3 months, as well as higher synaptic coverage at 5 months of age, supporting preserved neuropathological measures related to function. We further observed localised increases in tau pathology in the spinal cord and defined brain regions in young Stx6-/-;hTauP301S/P301S mice, despite total tau levels being comparable, in keeping with altered trafficking of pathological tau species with syntaxin-6 knockout. Despite a partial, early phenotypic rescue of functional measures, terminal endpoint comparisons were confounded by a 20% weight loss culling rule, as knockout mice maintained higher absolute weight. Taken together, this study functionally validates a role for syntaxin-6 in tauopathy pathogenesis, with syntaxin-6 knockout resulting in an early protective effect on multiple disease-relevant phenotypes in a humanised tauopathy model.

Invasive fungal infections (IFI) are a major cause of morbi-mortality, particularly in immunocompromised and critically ill patients. Increasing antifungal resistance, unequal access to diagnostics and therapies, and complex host-pathogen interactions highlight the need for coordinated research. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) addresses these challenges by promoting multidisciplinary collaboration and advancing research and education in medical mycology. This study aimed to characterize the global medical mycology workforce using EFISG as a representative international network. A cross-sectional survey was conducted among EFISG members between June and December 2025. The survey collected data on demographics, geographic distribution, professional background, career stage, research interests, language proficiency, and involvement in other scientific societies and ESCMID study groups. A total of 342 members from 72 countries responded, representing two thirds of all countries with EFISG membership. Most participants were based in Europe (60%). Sex distribution was balanced, and all career stages were included, with 22.8% early-career professionals and 14.6% trainees. Key research interests included epidemiology of fungal infections (68.4%), mycoses in immunocompromised hosts (67.5%), development of diagnostic methods (54.4%), and rare and emerging fungal diseases (54.1%). Infectious diseases specialists (52.3%) and microbiologists (42.4%) comprised the majority of respondents, and most reported active participation in other ESCMID study groups and scientific societies. These findings provide the first structured overview of the medical mycology workforce, identifying gaps in representation, training, and emerging research areas, with implications for global capacity building, collaboration, and strategic planning beyond EFISG. Invasive fungal infections are life-threatening, especially in immunocompromised patients. EFISG surveyed 342 members from 72 countries, revealing a diverse, multidisciplinary network. Findings guide research, collaboration, and education to improve prevention and care globally.

Common and rare genetic variants in leucine-rich repeat kinase 2 (LRRK2) have been linked with sporadic and familial Parkinson's disease (PD). Recently, we discovered that common genetic variation near the LRRK2 locus determined survival in progressive supranuclear palsy (PSP). Our study aimed to explore biomarkers of LRRK2 and lysosomal dysfunction in PSP. Immunoblotting was used to measure total LRRK2 and LRRK2-dependent Rab10 phosphorylation at the threonine 73 residue (pRab10Thr73) in neutrophil and monocyte samples from PSP and control participants. Urine samples were applied to a multiplexed assay to quantitate bis(monoacylglycerol)phosphate (BMP) species as markers of lysosomal dysfunction. Cerebrospinal fluid (CSF) samples from a wider cohort of PSP and control participants were applied to a stable isotope standards and capture by anti-peptide antibodies assay to measure total LRRK2 and pRab10Thr73 levels. LRRK2 genotypes (rs76904798 and rs2242367) and 1-year change in Progressive Supranuclear Palsy Rating Scale (PSPRS) scores were obtained. A total of 61 PSP and 34 control participants were included. Total urine 22:6-BMP levels were higher in PSP versus control samples (P = 0.04) and correlated with CSF total LRRK2 levels (r = 0.49, P = 0.04). There were no group-level differences in monocyte and CSF levels of total LRRK2 and pRab10Thr73. In PSP, carriers of the alternate allele (CT and TT genotypes) at the LRRK2 PD risk variant, rs76904798, had higher levels of CSF total LRRK2 versus CC genotype (P = 0.02). Baseline monocyte total LRRK2 levels predicted 1-year change in the PSPRS score (P = 0.008). Biochemically defined lysosomal dysfunction is evident in PSP. Genetic and biochemical stratification may identify PSP patients that would benefit from LRRK2-targeting therapies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Progressive supranuclear palsy (PSP) is a heterogeneous neurodegenerative disease characterised by the accumulation of misfolded 4-repeat tau within neurones and glial cells. There are limited longitudinal data on pathologically confirmed PSP patients with phenotypes other than classic Richardson's syndrome (RS) and the pathomechanisms responsible for the broad variability in clinical phenotype and progression are not well understood. An unresolved question in this context is whether distinct spatiotemporal patterns of tau pathology propagation exist within the clinicopathological spectrum of PSP. We included 241 consecutive, pathologically confirmed patients with PSP from the Queen Square Brain Bank for Neurological Disorders (2010-2022). Phenotyping was performed based on clinical features present within the first 3 years from symptom onset according to the Movement Disorder Society (MDS) criteria, and specific clinical features and disease milestones were recorded. Genotyping was performed using Illumina NeuroBooster and NeuroChip arrays and MAPT haplotype, APOE genotype, TRIM11 rs564309 and SLC2A13 rs2242367 single nucleotide polymorphism data were collated. Tissue sections from eight brain regions, mounted on glass slides, were immunostained for hyperphosphorylated tau and digitised using whole-slide scanning. Forty-one anatomical regions of interest were manually segmented, and total tau pathology burden was quantified using an automated, machine learning-based algorithm. The associations between survival and both clinicogenetic features and regional tau pathology burden were modelled using Cox regression and generalised linear models, respectively and the Subtype and Stage Inference (SuStaIn) algorithm was used to identify subgroups with distinct progression patterns. We have identified: (i) several clinical predictors of survival in PSP and the relationship between regional tau pathology burden and survival; (ii) novel anatomical reference standards for the expected distribution of tau pathology across MDS-defined PSP phenotypes, including region-specific white matter involvement in patients with corticobasal syndrome and speech/language variants; (iii) associations potentially linking biological sex, MAPT haplotype and TDP-43 co-pathology to clinical phenotype and regional tau pathology burden; (iv) patterns of covariance in regional tau pathology implicating inter-regional connectivity in tau spreading; and (v) three distinct spatiotemporal patterns of tau pathology progression: one characterised by initial involvement of subcortical grey matter followed by rostral spread to cortical regions and two characterised by early, simultaneous involvement of subcortical grey matter and cortical regions. Taken together, these results indicate that PSP clinicopathological heterogeneity is mediated by propagation of tau pathology along anatomically connected networks and via intrinsic regional susceptibility mechanisms, possibly influenced by sex, genetic factors and co-pathology.

This systematic review synthesizes prevalence rates and associated factors of intimate partner violence (IPV) against emerging adult women (aged 18-30) belonging to the Millennial and Generation Z cohorts. Following PRISMA guidelines, a search of Web of Science, PsycINFO and Scopus was conducted for the period between January 2013 and November 2025. Twenty-six studies from 20 high-income and 6 upper-middle-income Western countries met the inclusion criteria. Findings reveal significant methodological heterogeneity, with lifetime IPV prevalence ranging from 0.16% to 58.42% and 12-month rates from 5.1% to 33.6%. Notably, women aged 18 to 30 consistently ranked among the highest-prevalence groups, often exceeding WHO estimates despite shorter cumulative exposure. Psychological violence was the most prevalent subtype. Key associated factors included individual vulnerabilities (mental health, substance use, non-heterosexual orientation and childhood abuse), specific relational dynamics (economic dependence, "dirty dating," digital surveillance, breakup-reconciliation cycles and parenthood) and broader contexts such as neighbourhood deprivation, access to resources and help-seeking behaviour and the "Nordic Paradox" or backlash against gender equality. These findings highlight emerging adulthood as a critical period of vulnerability, necessitating targeted, generationally relevant interventions that address the unique developmental and digital risks of this cohort.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors with a prevalence of less than 0.05%. Being rather uncommon, they pose significant diagnostic challenges as the symptom complex is nonspecific. We present a clinical review based on the published literature and our center's experience in managing pheochromocytoma and paragangliomas over the past two decades. At the onset, summaries of three representative pheochromocytoma and paraganglioma cases are provided to highlight common diagnostic challenges. A holistic approach, combining biochemical evaluation with particular attention to pretest probability, accurate interpretation of imaging data, and differentiation from other adrenal masses, can aid in establishing the diagnosis and guiding appropriate management. Thus, the careful selection and interpretation of clinical, biochemical and imaging parameters are essential to improve diagnostic accuracy and optimize patient management.