Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes
AbstractExome-wide sequencing studies recently describedPTPN11 as a novel brain somatic epilepsy gene. In contrast, germline mutations ofPTPN11 are known to cause Noonan syndrome, a multisystem disorder characterized by abnormal facial features, developmental delay, and sporadically, also brain tumors. Herein, we performed a deep phenotype-genotype analysis of a comprehensive series of ganglioglioma (GG) with brain somatic alterations of thePTPN11/KRAS/NF1 genes compared to GG with common MAP-Kinase signaling pathway alterations, i.e.,BRAFV600E. Seventy-two GG were submitted to whole exome sequencing and genotyping and 84 ...
Source: Acta Neuropathologica - March 27, 2023 Category: Neurology Source Type: research
TREM2 gene expression associations with Alzheimer ’s disease neuropathology are region-specific: implications for cortical versus subcortical microglia
This study sought to correlate region-specificTREM2 mRNA expression with diverse neuropathological measures at autopsy using a large sample size (N = 945) of bulk RNA sequencing data from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP).TREM2 gene expression of the dorsolateral prefrontal cortex, posterior cingulate cortex, and caudate nucleus was assessed with respect to core pathology of Alzheimer ’s disease (amyloid-β, and tau), cerebrovascular pathology (cerebral infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), microglial activation (proportion of activated m...
Source: Acta Neuropathologica - March 25, 2023 Category: Neurology Source Type: research
Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer’s disease
AbstractCerebral amyloid- β (Aβ) accumulation due to impaired Aβ clearance is a pivotal event in the pathogenesis of Alzheimer’s disease (AD). Considerable brain-derived Aβ is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aβ and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aβ42 and 8.9% of Aβ40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aβ receptor LRP-1 expression down-regul ate...
Source: Acta Neuropathologica - March 25, 2023 Category: Neurology Source Type: research
TREM2 gene expression associations with Alzheimer ’s disease neuropathology are region-specific: implications for cortical versus subcortical microglia
This study sought to correlate region-specificTREM2 mRNA expression with diverse neuropathological measures at autopsy using a large sample size (N = 945) of bulk RNA sequencing data from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP).TREM2 gene expression of the dorsolateral prefrontal cortex, posterior cingulate cortex, and caudate nucleus was assessed with respect to core pathology of Alzheimer ’s disease (amyloid-β, and tau), cerebrovascular pathology (cerebral infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), microglial activation (proportion of activated m...
Source: Acta Neuropathologica - March 25, 2023 Category: Neurology Source Type: research
Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer’s disease
AbstractCerebral amyloid- β (Aβ) accumulation due to impaired Aβ clearance is a pivotal event in the pathogenesis of Alzheimer’s disease (AD). Considerable brain-derived Aβ is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aβ and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aβ42 and 8.9% of Aβ40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aβ receptor LRP-1 expression down-regul ate...
Source: Acta Neuropathologica - March 25, 2023 Category: Neurology Source Type: research
Cross- β helical filaments of Tau and TMEM106B in gray and white matter of multiple system tauopathy with presenile dementia
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 23, 2023 Category: Neurology Source Type: research
Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson ’s disease-related fibril polymorphism
AbstractLipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson’s disease (PD). However, it has not been fully determined which lipids are involved in the initiation of αSyn aggregation in PD. Here exploiting genetic understanding associating the loss-of-function mutation in Synapt ojanin 1 (SYNJ1), a phosphoinositide phosphatase, with familial PD and analysis of postmortem PD brains, we identified a novel lipid molecule involved in the toxic conversion of αSyn and its relation to PD. We first established a SYNJ1 knockout cell model and found SYNJ1 depletion increases the a...
Source: Acta Neuropathologica - March 20, 2023 Category: Neurology Source Type: research
Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions
AbstractGlioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors —distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealedATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially target...
Source: Acta Neuropathologica - March 18, 2023 Category: Neurology Source Type: research
Correction to: Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 17, 2023 Category: Neurology Source Type: research
Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy
AbstractSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by a loss of thesurvival of motor neuron 1 (SMN1) gene, resulting in a loss of spinal motor neurons (MNs), leading to muscle weakness and wasting. The pathogenesis of MN loss in SMA and the selective vulnerability in different cellular populations are not fully understood. To investigate the role of spinal astrocytes in the pathogenesis of late-onset SMA, we used a mouse model in addition to in vitro approaches. Immunostaining, Western blot analysis, small interfering ribonucleic acid (siRNA) transfections, functional assays, enzyme-link...
Source: Acta Neuropathologica - March 17, 2023 Category: Neurology Source Type: research
Correction to: Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - March 17, 2023 Category: Neurology Source Type: research
Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy
AbstractSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by a loss of thesurvival of motor neuron 1 (SMN1) gene, resulting in a loss of spinal motor neurons (MNs), leading to muscle weakness and wasting. The pathogenesis of MN loss in SMA and the selective vulnerability in different cellular populations are not fully understood. To investigate the role of spinal astrocytes in the pathogenesis of late-onset SMA, we used a mouse model in addition to in vitro approaches. Immunostaining, Western blot analysis, small interfering ribonucleic acid (siRNA) transfections, functional assays, enzyme-link...
Source: Acta Neuropathologica - March 17, 2023 Category: Neurology Source Type: research
