Plasma biomarkers for prediction of Alzheimer ’s disease neuropathologic change
AbstractWhile plasma biomarkers for Alzheimer ’s disease (AD) are increasingly being evaluated for clinical diagnosis and prognosis, few population-based autopsy studies have evaluated their utility in the context of predicting neuropathological changes. Our goal was to investigate the utility of clinically available plasma markers in predict ing Braak staging, neuritic plaque score, Thal phase, and overall AD neuropathological change (ADNC).We utilized a population-based prospective study of 350 participants with autopsy and antemortem plasma biomarker testing using clinically available antibody assay (Quanterix) consis...
Source: Acta Neuropathologica - June 3, 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 - June 1, 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 - June 1, 2023 Category: Neurology Source Type: research
The perils of contact sport: pathologies of diffuse brain swelling and chronic traumatic encephalopathy neuropathologic change in a 23-year-old rugby union player
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - June 1, 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 - June 1, 2023 Category: Neurology Source Type: research
Correction to: Dysregulation of astrocytic Ca2+ signaling and gliotransmitter release in mouse models of α-synucleinopathies
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - June 1, 2023 Category: Neurology Source Type: research
Correction: A novel subtype of sporadic Creutzfeldt –Jakob disease with PRNP codon 129MM genotype and PrP plaques
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - May 30, 2023 Category: Neurology Source Type: research
Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis
AbstractMultiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its re...
Source: Acta Neuropathologica - May 27, 2023 Category: Neurology Source Type: research
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson ’s disease
AbstractParkinson ’s Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system ( CNS). GAL3 ...
Source: Acta Neuropathologica - May 18, 2023 Category: Neurology Source Type: research
SCA34 caused by ELOVL4 L168F mutation is a lysosomal lipid storage disease sharing pathology features with neuronal ceroid lipofuscinosis and peroxisomal disorders
AbstractSpinocerebellar ataxia 34 (SCA34) is a late-onset progressive ataxia caused by a mutation inELOVL4, a gene involved in the biosynthesis of very long-chain fatty acids (VLCFAs). We performed post-mortem neuropathological examinations on four SCA34 patients with theELOVL4 L168F mutation and compared the findings to age-matched controls. Specific gross findings of SCA34 were limited to pontocerebellar atrophy. On light microscopy, pontine base showed neuronal loss and storage of an autofluorescent lipopigment positive on oil red O, PAS and Hale ’s colloidal iron and negative on Alcian blue and Luxol fast blue (LFB)....
Source: Acta Neuropathologica - May 15, 2023 Category: Neurology Source Type: research
