Correction: Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N-truncted Abeta in sporadic Alzheimer disease cases and mouse models
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 25, 2024 Category: Neurology Source Type: research
Disentangling and quantifying the relative cognitive impact of concurrent mixed neurodegenerative pathologies
AbstractNeurodegenerative pathologies such as Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and cerebrovascular disease (CVD) frequently coexist, but little is known about the exact contribution of each pathology to cognitive decline and dementia in subjects with mixed pathologies. We explored the relative cognitive impact of concurrent common and rare neurodegenerative pathologies employing multivariate logistic regression analysis adjusted for age, gender, and level of education. We analyzed a cohort of 6,26...
Source: Acta Neuropathologica - March 23, 2024 Category: Neurology Source Type: research
Gene transcript fusions are associated with clinical outcomes and molecular groups of meningiomas
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 20, 2024 Category: Neurology Source Type: research
Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia
AbstractThe stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson ’s disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on STING within immune cells, little is known about STING within neurons. Here, we document neuronal activation of the STING pathway in human postmortem cortical and spinal motor neurons from individuals affected by familial or sporadic ALS. This process takes place selectively in the most vulnerable cortical and spinal motor neurons but not in neurons that are less affected by the disease. Concordant STING a...
Source: Acta Neuropathologica - March 13, 2024 Category: Neurology Source Type: research
Role of GBA variants in Lewy body disease neuropathology
AbstractRare and commonGBA variants are risk factors for both Parkinson ’s disease (PD) and dementia with Lewy bodies (DLB). However, the degree to whichGBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rareGBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putam...
Source: Acta Neuropathologica - March 12, 2024 Category: Neurology Source Type: research
MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons
In this study, we investigated the impact of MSUT2 on tau pathogenesis using tau seeding models. Our findings indicate t hat the loss of MSUT2 mitigates human tau seed-induced pathology in neuron cultures and mouse models. In addition, MSUT2 regulates many gene transcripts, including the Adenosine Receptor 1 (A1AR), and we show that down regulation or inhibition of A1AR modulates the activity of the “ArfGAP with SH3 Domain, Ankyrin Repeat, and PH Domain 1 protein” (ASAP1), thereby influencing the internalization of pathogenic tau seeds into neurons resulting in reduction of tau pathology. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 12, 2024 Category: Neurology Source Type: research
Alteration of LARGE1 abundance in patients and a mouse model of 5q-associated spinal muscular atrophy
AbstractSpinal muscular atrophy (SMA) is a neuromuscular disorder caused by recessive pathogenic variants affecting the survival of motor neuron (SMN1) gene (localized on 5q). In consequence, cells lack expression of the corresponding protein. This pathophysiological condition is clinically associated with motor neuron (MN) degeneration leading to severe muscular atrophy. Additionally, vulnerability of other cellular populations and tissues including skeletal muscle has been demonstrated. Although the therapeutic options for SMA have considerably changed, treatment responses may differ thus underlining the persistent need ...
Source: Acta Neuropathologica - March 12, 2024 Category: Neurology Source Type: research
Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson ’s disease
AbstractParkinson ’s disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research—l-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples...
Source: Acta Neuropathologica - March 11, 2024 Category: Neurology Source Type: research
The prevalence and topography of spinal cord demyelination in multiple sclerosis: a retrospective study
AbstractSpinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. The demyelinated lesion is a cardinal feature. The well-characterised anatomy of the spinal cord and new analytic approaches allows the systematic study of lesion topography and its extent of inflammatory activity unveiling new insights into disease pathogenesis. We studied cervical, thoracic, and lumbar spinal cord tissue from 119 pathologically confirmed multiple sclerosis cases. Immunohistochemistry was used to detect demyelination (PLP) and classify lesional inflammatory activity (CD68). Prevalence and dis...
Source: Acta Neuropathologica - March 9, 2024 Category: Neurology Source Type: research
RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS
AbstractTDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped humanpost-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection ofStathmin-2 (STMN-2) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical...
Source: Acta Neuropathologica - March 5, 2024 Category: Neurology Source Type: research
Methylation class oligosarcoma, IDH-mutant could exhibit astrocytoma-like molecular features
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 5, 2024 Category: Neurology Source Type: research
Astroglial calcium signaling and homeostasis in tuberous sclerosis complex
This study investigates the intricate interplay between altered Ca2+ dynamics, mTOR pathway dysregulation, and cellular metabolism in astrocytes. The transcriptional profile of TSC patients revealed significant alterations in pathways associated with cellular respiration, ER and mitochondria, and Ca2+ regulation. TSC astrocytes exhibited lack of responsiveness to various stimuli, compromised oxygen consumption rate and reserve respiratory capacity underscoring their reduced capacity to react to environmental changes or cellular stress. Furthermore, our study revealed significant reduction of store operated calcium entry (S...
Source: Acta Neuropathologica - February 28, 2024 Category: Neurology Source Type: research
Disruption of the blood –brain barrier is correlated with spike endocytosis by ACE2 + endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on & quot;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 - February 27, 2024 Category: Neurology Source Type: research
Myofiber-type-dependent ‘boulder’ or ‘multitudinous pebble’ formations across distinct amylopectinoses
We present evidence of polyglucosan body size-dependent cell necrosis. We show that sex influences amylopectinosis in genotype, brain region and myofiber-type-specific fashion. RBCK1 is a component of the l inear ubiquitin chain assembly complex (LUBAC), the only known cellular machinery for head-to-tail linear ubiquitination critical to numerous cellular pathways. We show that the amylopectinosis of RBCK1 deficiency is not due to loss of linear ubiquitination, and that another function of RBCK1 or LUB AC must exist and operate in the shaping of glycogen. This work opens multiple new avenues toward understanding the struct...
Source: Acta Neuropathologica - February 27, 2024 Category: Neurology Source Type: research
Cortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE
AbstractChronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions ...
Source: Acta Neuropathologica - February 26, 2024 Category: Neurology Source Type: research
