Limbic-predominant age-related TDP-43 proteinopathy (LATE-NC) is associated with abundant TMEM106B pathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 12, 2023 Category: Neurology Source Type: research
Correction: Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 12, 2023 Category: Neurology Source Type: research
Limbic-predominant age-related TDP-43 proteinopathy (LATE-NC) is associated with abundant TMEM106B pathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 12, 2023 Category: Neurology Source Type: research
Correction: Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 12, 2023 Category: Neurology Source Type: research
A novel subtype of sporadic Creutzfeldt –Jakob disease with PRNP codon 129MM genotype and PrP plaques
AbstractThe presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt –Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrPD type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrPD T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (pGM) or ...
Source: Acta Neuropathologica - May 8, 2023 Category: Neurology Source Type: research
Tau seeds occur before earliest Alzheimer ’s changes and are prevalent across neurodegenerative diseases
This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer’s disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define d isease subtypes. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 8, 2023 Category: Neurology Source Type: research
A novel subtype of sporadic Creutzfeldt –Jakob disease with PRNP codon 129MM genotype and PrP plaques
AbstractThe presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt –Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrPD type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrPD T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (pGM) or ...
Source: Acta Neuropathologica - May 8, 2023 Category: Neurology Source Type: research
Tau seeds occur before earliest Alzheimer ’s changes and are prevalent across neurodegenerative diseases
This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer’s disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define d isease subtypes. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 8, 2023 Category: Neurology Source Type: research
Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes
AbstractFrontotemporal lobar degeneration (FTLD) is an umbrella term describing the neuropathology of a clinically, genetically and pathologically heterogeneous group of diseases, including frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). Among the major FTLD pathological subgroups, FTLD with TDP-43 positive inclusions (FTLD-TDP) and FTLD with tau-positive inclusions (FTLD-tau) are the most common, representing about 90% of the cases. Although alterations in DNA methylation have been consistently associated with neurodegenerative diseases, including Alzheimer ’s disease and Parkinson’s disease, l...
Source: Acta Neuropathologica - May 7, 2023 Category: Neurology Source Type: research
Progranulin deficiency results in sex-dependent alterations in microglia in response to demyelination
AbstractHeterozygous mutations in thegranulin (GRN) gene, resulting in the haploinsufficiency of the progranulin (PGRN) protein, is a leading cause of frontotemporal lobar degeneration (FTLD). Complete loss of the PGRN protein causes neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disorder. Polymorphisms in theGRN gene have also been associated with several other neurodegenerative diseases, including Alzheimer ’s disease (AD), and Parkinson’s disease (PD). PGRN deficiency has been shown to cause myelination defects previously, but how PGRN regulates myelination is unknown. Here, we report that PGRN deficiency...
Source: Acta Neuropathologica - April 30, 2023 Category: Neurology Source Type: research
AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model
AbstractHereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants inAMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncatingAMFR variants, resulting in a cohort of 20 in...
Source: Acta Neuropathologica - April 29, 2023 Category: Neurology Source Type: research
Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation
AbstractTREM2 is an innate immune receptor expressed by microglia in the adult brain. Genetic variation in theTREM2 gene has been implicated in risk for Alzheimer ’s disease and frontotemporal dementia, while homozygousTREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD). Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood. Here, we investigate the mechanisms by which a homozygous stop-gainTREM2 mutation (p.Q33X) contributes to NHD. Induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) were generated from two NHD families: three homozygousTREM2 p.Q33...
Source: Acta Neuropathologica - April 28, 2023 Category: Neurology Source Type: research
Correction to: Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - April 28, 2023 Category: Neurology Source Type: research
Transcriptome analysis stratifies second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes
AbstractMedulloblastoma (MB), one of the most common malignant pediatric brain tumor, is a heterogenous disease comprised of four distinct molecular groups (WNT, SHH, Group 3, Group 4). Each of these groups can be further subdivided into second-generation MB (SGS MB) molecular subgroups, each with distinct genetic and clinical characteristics. For instance, non-WNT/non-SHH MB (Group 3/4) can be subdivided molecularly into eight distinct and clinically relevant tumor subgroups. A further molecular stratification/summarization of these SGS MB would allow for the assignment of patients to risk-associated treatment protocols. ...
Source: Acta Neuropathologica - April 24, 2023 Category: Neurology Source Type: research
Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
AbstractHomozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using a...
Source: Acta Neuropathologica - April 24, 2023 Category: Neurology Source Type: research
