Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology?

The major pathological feature of Parkinson 's disease (PD), the second most common neurodegenerative disease and most common movement disorder, is the predominant degeneration of dopaminergic neurons in the substantia nigra, a part of the midbrain. Despite decades of research, the molecular mechanisms of the origin of the disease remain unknown. While the disease was initially viewed as a purely neuronal disorder, results from single-cell transcriptomics have suggested that oligodendrocytes may play an important role in the early stages of Parkinson's.

Tract-specific white matter hyperintensities and neuropsychiatric syndromes: a multicentre memory clinic study.

Background: White matter hyperintensities (WMH) have been implicated in the pathogenesis of neuropsychiatric symptoms of dementia but the functional significance of WMH in specific white matter (WM) tracts is unclear. We investigate whether WMH burden within major WM fibre classes and individual WM tracts are differentially associated with different neuropsychiatric syndromes in a large multicentre study.

Method: Neuroimaging and neuropsychiatric data of seven memory clinic cohorts through the Meta VCI Map consortium were harmonised.

Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults.

In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup.

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Multicentre prospective, randomised open-label, endpoint-blinded study to evaluate the safety and efficacy of propranolol for the prevention of stroke-associated pneumonia in patients with intracerebral haemorrhage (PROCHASE): rationale and design.

Background: Stroke-induced transient immune suppression is believed to contribute to post-stroke infections. The β-adrenergic receptor antagonist, propranolol, has been shown to prevent stroke-associated pneumonia (SAP) via reversing post-stroke immunosuppression in preclinical studies and in retrospective analysis in stroke patients. However, whether propranolol can reduce the risk of SAP has not been tested in prospective, randomised controlled trials.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Stroke recurrence and all-causemortality in CPAP-treated sleep-disordered-breathing patients.

Background: Obstructive sleep apnea (OSA) affects about 70 % of stroke patients and is closely linked to stroke development. It is unclear whether treatment with continuous positive airway pressure (CPAP) reduces the risk of stroke recurrence or mortality in post-stroke patients, partly due to limited follow-up time and small sample sizes of previous studies. To close this knowledge gap, this study investigated changes in stroke recurrence and mortality among CPAP-treated post-stroke patients with sleep-disordered breathing.

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.

Impact of fixation duration on messenger RNA detectability in human formalin-fixed paraffin-embedded brain tissue.

Technologies to study mRNA in post-mortem human brain samples have greatly advanced our understanding of brain pathologies. With ongoing improvements, particularly in formalin-fixed paraffin-embedded tissue, these technologies will continue to enhance our knowledge in the future. Despite various considerations for tissue and mRNA quality, such as pre-mortem health status and RNA integrity, the impact of the tissue fixation time has not been addressed in a systemic fashion yet.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI.

Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.

Do Amyloid Cerebral Deposits Influence the Long-Term Poststroke Cognitive Outcome?: The IDEA3 Study.

Background: Although the presence of amyloid deposits is associated with a more severe cognitive status in patients with stroke at baseline, its influence on the subsequent cognitive outcome has not been extensively assessed. The primary objective of the present study of the IDEA3 (Imagerie des dépôts amyloïdes cérébraux par florbetapir AV-45 et diagnostic des déficits cognitifs et démence post Accident Vasculaire Cérébral) cohort was to determine the influence of amyloid positron emission tomography (PET) status on the 5-year cognitive outcome.

Methods: This longitudinal study performed in Amiens University Hospital (inclusions: October 2014 to October 2019; last visits: October 2018 to February 2023) has included 91 patients with stroke (ischemic stroke, 89%; hemorrhagic stroke, 11%) with florbetapir PET data at baseline (positive, n=14).

Mef2c Exacerbates Neuron Necroptosis via Modulating Alternative Splicing of Cflar in Ischemic Stroke With Hyperlipidemia.

Aim: Hyperlipidemia is a common comorbidity of stroke patients, elucidating the mechanism that underlies the exacerbated ischemic brain injury after stroke with hyperlipidemia is emerging as a significant clinical problem due to the growing proportion of hyperlipidemic stroke patients.

Methods: Mice were fed a high-fat diet for 12 weeks to induce hyperlipidemia. Transient middle cerebral artery occlusion was induced as a mouse model of ischemic stroke.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes.

Aβ status assessment in a hypothetical scenario prior to treatment with disease-modifying therapies: Evidence from 10-year real-world experience at university memory clinics.

Introduction: With the advent of disease-modifying therapies, accurate assessment of biomarkers indicating the presence of disease-associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography (Aβ PET) biomarkers in a real-world memory-clinic setting to develop an efficient algorithm for clinical use.

Methods: Patients were evaluated for AD-related Aβ pathology from two independent cohorts (Ludwig Maximilian University [LMU],  = 402, and Medical University of Vienna [MUV],  = 144).

Endovascular therapy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage: Single-center experience in a high-volume neurovascular unit.

Introduction: Despite targeted standard therapy, aneurysmal subarachnoid hemorrhage (aSAH) frequently leads to cerebral vasospasms (CVS) of large cerebral arteries, reduced oxygen supply of brain tissue, known as delayed cerebral ischemia (DCI), subsequent development of manifest cerebral infarction and poor neurological outcome.

Research Question: The primary aim was to evaluate the efficacy of endovascular spasmolysis (eSL) as a rescue therapy for delayed ischemic neurological deficits (DIND) occurring despite maximum conservative treatment, with the potential benefit of preventing permanent ischemic deficits, and thus, improving overall neurological outcomes.

Material And Methods: In our retrospective, monocentric study, we included 310 patients developing CVS during hospitalization and evaluated their clinical and radiographic outcomes.

Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies.

Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients.

Probe set selection for targeted spatial transcriptomics.

Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design).

White matter aging and its impact on brain function.

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders.