Myeloid cell iron uptake pathways and paramagnetic rim formation in multiple sclerosis
AbstractIn multiple sclerosis (MS), sustained inflammatory activity can be visualized by iron-sensitive magnetic resonance imaging (MRI) at the edges of chronic lesions. These paramagnetic rim lesions (PRLs) are associated with clinical worsening, although the cell type-specific and molecular pathways of iron uptake and metabolism are not well known. We studied two postmortem cohorts: an exploratory formalin-fixed paraffin-embedded (FFPE) tissue cohort of 18 controls and 24 MS cases and a confirmatory snap-frozen cohort of 6 controls and 14 MS cases. Besides myelin and non-heme iron imaging, the haptoglobin-hemoglobin scav...
Source: Acta Neuropathologica - September 16, 2023 Category: Neurology Source Type: research
Correction to: Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - September 12, 2023 Category: Neurology Source Type: research
The choroidal nervous system: a link between mineralocorticoid receptor and pachychoroid
AbstractCentral serous chorioretinopathy (CSCR) belongs to the pachychoroid spectrum, a pathological phenotype of the choroidal vasculature, in which blood flow is under the choroidal nervous system (ChNS) regulation. The pathogenesis of CSCR is multifactorial, with the most recognised risk factor being intake of glucocorticoids, which activate both the gluco- and the mineralocorticoid (MR) receptors. As MR over-activation is pathogenic in the retina and choroid, it could mediate the pathogenic effects of glucocorticoids in CSCR. But the role of MR signalling in pachychoroid is unknown and whether it affects the ChNS has n...
Source: Acta Neuropathologica - September 8, 2023 Category: Neurology Source Type: research
Integrative multi-omics reveals two biologically distinct groups of pilocytic astrocytoma
AbstractPilocytic astrocytoma (PA), the most common pediatric brain tumor, is driven by aberrant mitogen-activated protein kinase signaling most commonly caused byBRAF gene fusions or activating mutations. While 5-year overall survival rates exceed 95%, tumor recurrence or progression constitutes a major clinical challenge in incompletely resected tumors. Here, we used similarity network fusion (SNF) analysis in an integrative multi-omics approach employing RNA transcriptomic and mass spectrometry-based proteomic profiling to molecularly characterize PA tissue samples from 62 patients. Thereby, we uncovered that PAs segreg...
Source: Acta Neuropathologica - September 1, 2023 Category: Neurology Source Type: research
Microglial contribution to the pathology of neurodevelopmental disorders in humans
AbstractMicroglia are the brain ’s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopme ntal processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involve...
Source: Acta Neuropathologica - September 1, 2023 Category: Neurology Source Type: research
Analysis of inflammatory markers and tau deposits in an autopsy series of nine patients with anti-IgLON5 disease
AbstractAnti-IgLON5 disease is a rare neurological, probably autoimmune, disorder associated in many cases with a specific tauopathy. Only a few post-mortem neuropathological studies have been reported so far. Little is known about the pathogenic mechanisms that result in neurodegeneration. We investigated the neuropathology of anti-IgLON5 disease and characterized cellular and humoral inflammation. We included nine cases (six of them previously published). Median age of patients was 71 years (53–82 years), the median disease duration was 6 years (0.5–13 years), and the female to male ratio was 5:4. Six cases with...
Source: Acta Neuropathologica - August 30, 2023 Category: Neurology Source Type: research
Detection of blood –brain barrier disruption in brains of patients with COVID-19, but no evidence of brain penetration by SARS-CoV-2
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 25, 2023 Category: Neurology Source Type: research
TDP-43 pathology in the retina of patients with frontotemporal lobar degeneration
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 19, 2023 Category: Neurology Source Type: research
Correction: APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer ’s disease
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 17, 2023 Category: Neurology Source Type: research
Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice
Conclusions: Neuronal tau pathology differentially exacerbated CC pathology based on i njury severity and chronicity. Ongoing CC atrophy from s-TBI became accompanied by late demyelination. Pathological tau significantly worsened CC atrophy during the chronic phase after r-mTBI. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 14, 2023 Category: Neurology Source Type: research
Spatial immune profiling of glioblastoma identifies an inflammatory, perivascular phenotype associated with longer survival
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 13, 2023 Category: Neurology Source Type: research
The variance in phosphorylated, insoluble ⍺-synuclein in humans, rats, and mice is not mainly driven by biological sex
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 11, 2023 Category: Neurology Source Type: research
TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that prima...
Source: Acta Neuropathologica - August 9, 2023 Category: Neurology Source Type: research
Inflammation and the pathological progression of Alzheimer ’s disease are associated with low circulating choline levels
AbstractDeficiency of dietary choline, an essential nutrient, is observed worldwide, with ~ 90% of Americans being deficient. Previous work highlights a relationship between decreased choline intake and an increased risk for cognitive decline and Alzheimer’s disease (AD). The associations between blood circulating choline and the pathological progression in both mild cognitive impair ment (MCI) and AD remain unknown. Here, we examined these associations in a cohort of patients with MCI with presence of either sparse or high neuritic plaque density and Braak stage and a second cohort with either moderate AD (moderat...
Source: Acta Neuropathologica - August 7, 2023 Category: Neurology Source Type: research
Decreased dystrophin expression and elevated dystrophin-targeting miRNAs in anti-HMGCR immune-mediated necrotizing myopathy
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 5, 2023 Category: Neurology Source Type: research
