Brain age in genetic and idiopathic Parkinson's disease.

The brain-age gap, i.e. the difference between the brain age estimated from structural MRI data and the chronological age of an individual, has been proposed as a summary measure of brain integrity in neurodegenerative diseases.

Phosphatidylethanolamines are the Main Lipid Class Altered in Red Blood Cells from Patients with VPS13A Disease/Chorea-Acanthocytosis.

Background: VPS13A disease is an ultra-rare disorder caused by loss of function mutations in VPS13A characterized by striatal degeneration and by red blood cell (RBC) acanthocytosis. VPS13A is a bridge-like protein mediating lipid transfer at membrane contact sites.

Objectives: To assess the lipid composition of patient-derived RBCs.

Artificial intelligence-based rapid brain volumetry substantially improves differential diagnosis in dementia.

Introduction: This study evaluates the clinical value of a deep learning-based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age- and sex-adjusted percentile comparisons.

Methods: Fifty-five patients-17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls-underwent cranial magnetic resonance imaging scans. Two board-certified neuroradiologists (BCNR), two board-certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance.

Axonal transcriptome reveals upregulation of PLK1 as a protective mechanism in response to increased DNA damage in FUS spinal motor neurons.

Mutations in the gene ( ) are among the most frequently occurring genetic forms of amyotrophic lateral sclerosis (ALS). Early pathogenesis of -ALS involves impaired DNA damage response and axonal degeneration. However, it is still poorly understood how these gene mutations lead to selective spinal motor neuron (MN) degeneration and how nuclear and axonal phenotypes are linked.

Upregulated miR-10b-5p as a potential miRNA signature in amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset disease marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Death in most patients usually occurs within 2-4 years after symptoms onset. Despite promising progress in delineating underlying mechanisms, such as disturbed proteostasis, DNA/RNA metabolism, splicing or proper nucleocytoplasmic shuttling, there are no effective therapies for the vast majority of cases.

Novel Biallelic Synonymous Exonic Variant in Affecting mRNA Splicing: Case Report.

Objectives: Chorea-acanthocytosis is an autosomal recessively inherited condition caused by loss-of-function pathogenic variants in . We identified a novel synonymous exonic variant leading to abnormal mRNA splicing in a patient with chorea-acanthocytosis.

Methods: A patient with focal epilepsy developed generalized chorea with orolingual dystonia, cognitive decline, and peripheral neuropathy, consistent with chorea-acanthocytosis.

Synthesis of NaWH and NaReH Ternary Hydrides at High Pressures.

The Na-W-H and Na-Re-H ternary systems were studied in a diamond anvil cell through X-ray diffraction and Raman spectroscopy, supported by density functional theory and molecular dynamics calculations. NaWH can be synthesized above 7.8 GPa and 1400 K, remaining stable between at least 0.

HoLLiECares - Development of a multi-functional robot for professional care.

Germany's healthcare sector suffers from a shortage of nursing staff, and robotic solutions are being explored as a means to provide quality care. While many robotic systems have already been established in various medical fields (e.g.

Mitochondrial DNA replication is essential for neurogenesis but not gliogenesis in fetal neural stem cells.

Mitochondria are unique organelles that have their own genome (mtDNA) and perform various pivotal functions within a cell. Recently, evidence has highlighted the role of mitochondria in the process of stem cell differentiation, including differentiation of neural stem cells (NSCs). Here we studied the importance of mtDNA function in the early differentiation process of NSCs in two cell culture models: the CGR8-NS cell line that was derived from embryonic stem cells by a lineage selection technique, and primary NSCs that were isolated from embryonic day 14 mouse fetal forebrain.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.

Objective: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates.

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy.

Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated guanine exchange factor Plekhg5 drives the UPS of Sod1.

Structural phase transition in NH₄F under extreme pressure conditions.

Ammonium fluoride (NH₄F) exhibits a variety of crystalline phases depending on temperature and pressure. By employing Raman spectroscopy and synchrotron X-ray diffraction beyond megabar pressures (up to 140 GPa), we have here observed a novel dense solid phase of NH₄F, characterised by the tetragonal P4/nmm structure also observed in other ammonium halides under less extreme pressure conditions, typically a few GPa. Using detailed ab-initio calculations and reevaluating earlier theoretical models pertaining to other ammonium halides, we examine the microscopic mechanisms underlying the transition from the low-pressure cubic phase (P-43m) to the newly identified high-pressure tetragonal phase (P4/nmm).

Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.

Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis.

Risk willingness in multiple system atrophy and Parkinson's disease understanding patient preferences.

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.

Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis.

Background: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.

Methods: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich).

Patients' and caregivers' perception of multidimensional and palliative care in amyotrophic lateral sclerosis - protocol of a German multicentre study.

Introduction: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS).

Predicted hot superconductivity in LaScH under pressure.

The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH, YH, YH, and LaH) with superconducting critical temperatures () well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

Cerebral glucose metabolic correlates of cognitive and behavioural impairments in amyotrophic lateral sclerosis.

Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results.

Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi).

Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.

Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of (SOD1)- and in particular (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1.

Increased Vulnerability to Ferroptosis in FUS-ALS.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exists, e.g.