The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments
AbstractThis review recounts the definitions and research evidence supporting the multifaceted roles of neuroinflammation in the injured brain following trauma. We summarise the literature fluctuating from the protective and detrimental properties that cytokines, leukocytes and glial cells play in the acute and chronic stages of TBI, including the intrinsic factors that influence cytokine responses and microglial functions relative to genetics, sex, and age. We elaborate on the pros and cons that cytokines, chemokines, and microglia play in brain repair, specifically neurogenesis, and how such conflicting roles may be harn...
Source: Acta Neuropathologica - December 7, 2018 Category: Neurology Source Type: research

Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology
AbstractTAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Here, we examined TDP-43 pathobiology within these vulnerable neurons in t...
Source: Acta Neuropathologica - December 3, 2018 Category: Neurology Source Type: research

Enteric alpha-synuclein expression is increased in Crohn ’s disease
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 30, 2018 Category: Neurology Source Type: research

Current state of Alzheimer ’s fluid biomarkers
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical tria ls. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific conte xt of ...
Source: Acta Neuropathologica - November 28, 2018 Category: Neurology Source Type: research

Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies
AbstractThe inadvertent transmission of long incubating, untreatable and fatal neurodegenerative prionopathies, notably iatrogenic Creutzfeldt –Jakob disease, following transplantation of cadaver-derived corneas, pituitary growth, hormones and dura mater, constitutes a historical precedent which has underpinned the application of precautionary principles to modern day advanced cell therapies. To date these have been reflected by geograph ic or medical history risk-based deferral of tissue donors. Emergent understanding of other prion-like proteinopathies, their potential independence from prions as a transmissible ag...
Source: Acta Neuropathologica - November 27, 2018 Category: Neurology Source Type: research

Post-stroke inflammation —target or tool for therapy?
AbstractInflammation is currently considered a prime target for the development of new stroke therapies. In the acute phase of ischemic stroke, microglia are activated and then circulating immune cells invade the peri-infarct and infarct core. Resident and infiltrating cells together orchestrate the post-stroke inflammatory response, communicating with each other and the ischemic neurons, through soluble and membrane-bound signaling molecules, including cytokines. Inflammation can be both detrimental and beneficial at particular stages after a stroke. While it can contribute to expansion of the infarct, it is also responsi...
Source: Acta Neuropathologica - November 27, 2018 Category: Neurology Source Type: research

The role of de novo mutations in adult-onset neurodegenerative disorders
AbstractThe genetic underpinnings of the most common adult-onset neurodegenerative disorders (AOND) are complex in majority of the cases. In some families, however, the disease can be inherited in a Mendelian fashion as an autosomal-dominant trait. Next to that, patients carrying mutations in the same disease genes have been reported despite a negative family history. Although challenging to demonstrate due to the late onset of the disease in most cases, the occurrence of de novo mutations can explain this sporadic presentation, as demonstrated for severe neurodevelopmental disorders. Exome or genome sequencing of patient ...
Source: Acta Neuropathologica - November 26, 2018 Category: Neurology Source Type: research

Inflammation in ALS/FTD pathogenesis
AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that overlap in their clinical presentation, pathology and genetics, and likely represent a spectrum of one underlying disease. In ALS/FTD patients, neuroinflammation characterized by innate immune responses of tissue-resident glial cells is uniformly present on end-stage pathology, and human imaging studies and rodent models support that neuroinflammation begins early in disease pathogenesis. Additionally, changes in circulating immune cell populations and cytokines are found in ALS/FTD patients, and there is evide...
Source: Acta Neuropathologica - November 21, 2018 Category: Neurology Source Type: research

TIA1 regulates the generation and response to toxic tau oligomers
AbstractRNA binding proteins (RBPs) are strongly linked to the pathophysiology of motor neuron diseases. Recent studies show that RBPs, such as TIA1, also contribute to the pathophysiology of tauopathy. RBPs co-localize with tau pathology, and reduction of TIA1 protects against tau-mediated neurodegeneration. The mechanism through which TIA1 reduction protects against tauopathy, and whether TIA1 modulates the propagation of tau, are unknown. Previous studies indicate that the protective effect of TIA1 depletion correlates with both the reduction of oligomeric tau and the reduction of pathological TIA1 positive tau inclusio...
Source: Acta Neuropathologica - November 21, 2018 Category: Neurology Source Type: research

Chromosome arm 1q gain is an adverse prognostic factor in localized and diffuse leptomeningeal glioneuronal tumors with BRAF gene fusion and 1p deletion
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 21, 2018 Category: Neurology Source Type: research

Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA
AbstractBrainstem gliomas are molecularly heterogeneous diseases, many of which are difficult to safely surgically resect and have limited treatment options due to their eloquent location. These constraints pose challenges to biopsy, which limits the use of routine molecular profiling and identification of personalized therapies. Here, we explored the potential of sequencing of circulating tumor DNA (ctDNA) isolated from the cerebrospinal fluid (CSF) of brainstem glioma patients as a less invasive approach for tumor molecular profiling. CSF was obtained from patients either intraoperatively (91.2%, 52/57), from ventricular...
Source: Acta Neuropathologica - November 20, 2018 Category: Neurology Source Type: research

Mitochondria, ER, and nuclear membrane defects reveal early mechanisms for upper motor neuron vulnerability with respect to TDP-43 pathology
AbstractInsoluble aggregates containing TDP-43 are widely observed in the diseased brain, and defined as “TDP-43 pathology” in a spectrum of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and ALS with frontotemporal dementia. Here we report that Betz cells of patients with TDP-43 pathology display a distinct set of intracellular defects especially at the site of nuclear membrane, mitochondria and endoplasmic reticulum (ER). Numerous TDP-43 mouse models have been generated to discern the cellular and molecular basis of the disease, but mechanisms of neuronal vu...
Source: Acta Neuropathologica - November 19, 2018 Category: Neurology Source Type: research

ETMR-like infantile cerebellar embryonal tumors in the extended morphologic spectrum of DICER1 -related tumors
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 16, 2018 Category: Neurology Source Type: research

Differential impact of pure glyphosate and glyphosate-based herbicide in a model of peripheral nervous system myelination
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 16, 2018 Category: Neurology Source Type: research

“When sex influences the brain: implications for Alzheimer disease”
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 15, 2018 Category: Neurology Source Type: research

The metalloprotease ADAMTS4 generates N-truncated A β4–x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer’s disease
AbstractBrain accumulation and aggregation of amyloid- β (Aβ) peptides is a critical step in the pathogenesis of Alzheimer’s disease (AD). Full-length Aβ peptides (mainly Aβ1–40 and Aβ1–42) are produced through sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, studies of autopsy brain sa mples from AD patients have demonstrated that a large fraction of insoluble Aβ peptides are truncated at the N-terminus, with Aβ4–x peptides being particularly abundant. Aβ4–x peptides are highly aggregatio...
Source: Acta Neuropathologica - November 13, 2018 Category: Neurology Source Type: research

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer ’s disease
AbstractCardiovascular (CV)- and lifestyle-associated risk factors (RFs) are increasingly recognized as important for Alzheimer ’s disease (AD) pathogenesis. Beyond the ε4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV-associated genes also increase risk for AD. Using large genome-wide association studies and validated  tools to quantify genetic overlap, we systematically identified single nucleotide polymorphisms (SNPs)jointly associated with AD and one or more CV-associated RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist ...
Source: Acta Neuropathologica - November 9, 2018 Category: Neurology Source Type: research

Inner ear pathologies impair sodium-regulated ion transport in Meniere ’s disease
AbstractMeniere ’s disease (MD), a syndromal inner ear disease, is commonly associated with a pathological accumulation of endolymphatic fluid in the inner ear, termed “idiopathic” endolymphatic hydrops (iEH). Although numerous precipitating/exacerbating factors have been proposed for MD, its etiology remains elusive. Here, using immunohistochemistry and in situ protein–protein interaction detection assays, we demonstrate mineralocorticoid-controlled sodium transport mechanisms in the epithelium of the extraosseous portion of the endolymphatic sac (eES) in the murine and human inner ears. Histologic...
Source: Acta Neuropathologica - November 2, 2018 Category: Neurology Source Type: research

Rare variants in the neuronal ceroid lipofuscinosis gene MFSD8 are candidate risk factors for frontotemporal dementia
AbstractPathogenic variation inMAPT,GRN, andC9ORF72 accounts for at most only half of frontotemporal lobar degeneration (FTLD) cases with a family history of neurological disease. This suggests additional variants and genes that remain to be identified as risk factors for FTLD. We conducted a case –control genetic association study comparing pathologically diagnosed FTLD patients (n = 94) to cognitively normal older adults (n = 3541), and found suggestive evidence that gene-wide aggregate rare variant burden inMFSD8 is associated with FTLD risk. Because homozygous mutations inMFSD8 cause n...
Source: Acta Neuropathologica - October 31, 2018 Category: Neurology Source Type: research

Chordoid meningiomas can be sub-stratified into prognostically distinct DNA methylation classes and are enriched for heterozygous deletions of chromosomal arm 2p
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 31, 2018 Category: Neurology Source Type: research

The aftermath of boxing revisited: identifying chronic traumatic encephalopathy pathology in the original Corsellis boxer series
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 30, 2018 Category: Neurology Source Type: research

Atypical parkinsonism of progressive supranuclear palsy –parkinsonism (PSP-P) phenotype with rare variants in FBXO7 and VPS35 genes associated with Lewy body pathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 29, 2018 Category: Neurology Source Type: research

C9orf72 -FTD/ALS pathogenesis: evidence from human neuropathological studies
AbstractWhat are the most important and treatable pathogenic mechanisms inC9orf72-FTD/ALS? Model-based efforts to address this question are forging ahead at a blistering pace, often with conflicting results. But what does the human neuropathological literature reveal? Here, we provide a critical review of the human studies to date, seeking to highlight key gaps or uncertainties in our knowledge. First, we engage theC9orf72-specific mechanisms, including C9orf72 haploinsufficiency, repeat RNA foci, and dipeptide repeat protein inclusions. We then turn to some of the most prominentC9orf72-associated features, such as TDP-43 ...
Source: Acta Neuropathologica - October 27, 2018 Category: Neurology Source Type: research

Evidence of intraneuronal A β accumulation preceding tau pathology in the entorhinal cortex
AbstractGrowing evidence gathered from transgenic animal models of Alzheimer ’s disease (AD) indicates that the intraneuronal accumulation of amyloid-β (Aβ) peptides is an early event in the AD pathogenesis, producing cognitive deficits before the deposition of insoluble plaques. Levels of soluble Aβ are also a strong indicator of synaptic deficits and concurrent AD neu ropathologies in post-mortem AD brain; however, it remains poorly understood how this soluble amyloid pool builds within the brain in the decades leading up to diagnosis, when a patient is likely most amenable to early therapeutic inter...
Source: Acta Neuropathologica - October 25, 2018 Category: Neurology Source Type: research

Questions concerning the role of amyloid- β in the definition, aetiology and diagnosis of Alzheimer’s disease
AbstractThe dominant hypothesis of Alzheimer ’s disease (AD) aetiology, the neuropathological guidelines for diagnosing AD and the majority of high-profile therapeutic efforts, in both research and in clinical practice, have been built around one possible causal factor, amyloid-β (Aβ). However, the causal link between Aβ and AD remains un proven. Here, in the context of a detailed assessment of historical and contemporary studies, we raise critical questions regarding the role of Aβ in the definition, diagnosis and aetiology of AD. We illustrate that a holistic view of the avai...
Source: Acta Neuropathologica - October 22, 2018 Category: Neurology Source Type: research

Sex differences in Alzheimer ’s disease and common neuropathologies of aging
AbstractAlzheimer ’s dementia is significantly more common in women than in men. However, few pathological studies have addressed sex difference in Alzheimer’s disease (AD) and other brain pathologies. We leveraged postmortem data from 1453 persons who participated in one of two longitudinal community-based studi es of older adults, the Religious Orders Study and the Rush Memory and Aging Project. Postmortem examination identified AD pathologies, neocortical Lewy bodies, DNA-binding protein 43 (TDP-43), hippocampal sclerosis, gross and micro infarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid an...
Source: Acta Neuropathologica - October 17, 2018 Category: Neurology Source Type: research

Correction to: Picomolar concentrations of oligomeric alpha-synuclein sensitizes TLR4 to play an initiating role in Parkinson ’s disease pathogenesis
In the original publication of this article, the author Magarida Rodrigues was written incorrectly. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 17, 2018 Category: Neurology Source Type: research

Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain
In this study, we aimed to elucidate the functional relationship between CSF efflux through lymphatics and the potential influx into the brain by assessment of the distribution of CSF-infused tracers in awake and anesthetized mice. Using near-infrared fluorescence imaging, we showed that tracers quickly exited the subarachnoid space by transport through the lymphatic system to the systemic circulation in awake mice, significantly limiting their spread to the paravascular spaces of the brain. Magnetic resonance imaging and fluorescence microscopy through the skull under anesthetized conditions indicated that tracers remaine...
Source: Acta Neuropathologica - October 10, 2018 Category: Neurology Source Type: research

Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis
AbstractMotor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise inhSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion-like properties also exist in human ALS. Aggregate seeds were prepared from...
Source: Acta Neuropathologica - October 3, 2018 Category: Neurology Source Type: research

Rebuttal to Drs. Grinberg and Heinsen
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 3, 2018 Category: Neurology Source Type: research

Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis
AbstractMotor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise inhSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion-like properties also exist in human ALS. Aggregate seeds were prepared from...
Source: Acta Neuropathologica - October 3, 2018 Category: Neurology Source Type: research

Rebuttal to Drs. Grinberg and Heinsen
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 3, 2018 Category: Neurology Source Type: research

Tau filaments from multiple cases of sporadic and inherited Alzheimer ’s disease adopt a common fold
AbstractThe ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer ’s disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determ ine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Physiological clearance of tau in the periphery and its therapeutic potential for tauopathies
AbstractAccumulation of pathological tau is the hallmark of Alzheimer ’s disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unkno wn. Here, we found that cisterna magna injected131I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than tho...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons
Abstractα-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-i...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Targeting pericytes for therapeutic approaches to neurological disorders
AbstractMany  central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood–brain barrier. Pericytes, an u nder-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood–brain barrier, capillary blood flow and the movement of immune cells into the brain. They also form part of the “glial” scar isolating dam...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Pediatric low-grade gliomas can be molecularly stratified for risk
In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLG...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways
AbstractMicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons in Alzheimer ’s disease. We demonstrate that miR-132 protects primary mouse and human wild-type neurons and more vulnerable Tau-mutant neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopat hies, promotes neurite elongation and branching, and reduces n...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Synapsin III deficiency hampers α-synuclein aggregation, striatal synaptic damage and nigral cell loss in an AAV-based mouse model of Parkinson’s disease
AbstractParkinson ’s disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of nigral dopamine neurons. The deposition of fibrillary aggregated α-synuclein in Lewy bodies (LB), that is considered to play a causative role in the disease, constitutes another key n europathological hallmark of PD. We have recently described that synapsin III (Syn III), a synaptic phosphoprotein that regulates dopamine release in cooperation with α-synuclein, is present in the α-synuclein insoluble fibrils composing the LB of patients affected by PD. Moreover, we obse...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson ’s models
AbstractAlpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson ’s disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mit ochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy. Partial red...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Tau filaments from multiple cases of sporadic and inherited Alzheimer ’s disease adopt a common fold
AbstractThe ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer ’s disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determ ine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Patterns and severity of vascular amyloid in Alzheimer ’s disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer’s disease
In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, betweenAPP genetic causes of AD (APPdup,APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer ’s disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vasc...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Estimation of amyloid distribution by [ 18 F]flutemetamol PET predicts the neuropathological phase of amyloid β-protein deposition
AbstractThe deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer’s disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactiv e-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18...
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Correction to: A suggestion to introduce the diagnosis of “diffuse midline glioma of the pons, H3 K27 wildtype (WHO grade IV)”
The citation of the original publication in PubMed contains an error. The seventh author name is wrongly cited. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 1, 2018 Category: Neurology Source Type: research

Structure and evolution of double minutes in diagnosis and relapse brain tumors
AbstractDouble minute chromosomes are extrachromosomal circular DNA fragments frequently found in brain tumors. To understand their evolution, we characterized the double minutes in paired diagnosis and relapse tumors from a pediatric high-grade glioma and four adult glioblastoma patients. We determined the full structures of the major double minutes using a novel approach combining multiple types of supporting genomic evidence. Among the double minutes identified in the pediatric patient, only one carryingEGFR was maintained at high abundance in both samples, whereas two others were present in only trace amounts at diagno...
Source: Acta Neuropathologica - September 28, 2018 Category: Neurology Source Type: research

cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - September 26, 2018 Category: Neurology Source Type: research

The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer ’s disease
AbstractSynaptic degeneration and neuronal loss are early events in Alzheimer ’s disease (AD), occurring long before symptom onset, thus making synaptic biomarkers relevant for enabling early diagnosis. The postsynaptic protein neurogranin (Ng) is a cerebrospinal fluid (CSF) biomarker for AD, also in the prodromal phase. Here we tested the hypothesis that during AD neurodeg eneration, processing of full-length Ng into endogenous peptides in the brain is increased. We characterized Ng in post-mortem brain tissue and investigated the levels of endogenous Ng peptides in relation to full-length protein in brain tissue of...
Source: Acta Neuropathologica - September 22, 2018 Category: Neurology Source Type: research