8,097 results match your criteria Acta neuropathologica[Journal]


Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons.

Acta Neuropathol 2018 Jul 11. Epub 2018 Jul 11.

Department of Neuroscience, The University of Minnesota, Minneapolis, MN, USA.

α-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. Read More

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July 2018
2 Reads

MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways.

Acta Neuropathol 2018 Jul 7. Epub 2018 Jul 7.

Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, 9006, Boston, MA, 02115, USA.

MicroRNAs (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. Read More

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FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma.

Acta Neuropathol 2018 Jul 5. Epub 2018 Jul 5.

Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.

Extraventricular neurocytoma (EVN) is a rare primary brain tumor occurring in brain parenchyma outside the ventricular system. Histopathological characteristics resemble those of central neurocytoma but exhibit a wider morphologic spectrum. Accurate diagnosis of these histologically heterogeneous tumors is often challenging because of the overlapping morphological features and the lack of defining molecular markers. Read More

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Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience.

Acta Neuropathol 2018 Jul 2. Epub 2018 Jul 2.

Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.

Recently, we described a machine learning approach for classification of central nervous system tumors based on the analysis of genome-wide DNA methylation patterns [6]. Here, we report on DNA methylation-based central nervous system (CNS) tumor diagnostics conducted in our institution between the years 2015 and 2018. In this period, more than 1000 tumors from the neurosurgical departments in Heidelberg and Mannheim and more than 1000 tumors referred from external institutions were subjected to DNA methylation analysis for diagnostic purposes. Read More

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July 2018
1 Read

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Acta Neuropathol 2018 Jul 2. Epub 2018 Jul 2.

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 1207 17th Avenue S, Nashville, TN, 37212, USA.

Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Read More

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July 2018
4 Reads

Pediatric low-grade gliomas can be molecularly stratified for risk.

Acta Neuropathol 2018 Jun 14. Epub 2018 Jun 14.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong SAR, China.

Pediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Read More

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June 2018
2 Reads

Nucleo-cytoplasmic transport of TDP-43 studied in real time: impaired microglia function leads to axonal spreading of TDP-43 in degenerating motor neurons.

Acta Neuropathol 2018 Jun 25. Epub 2018 Jun 25.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Centre for Motor Neuron Disease Research, Macquarie University, Sydney, NSW, Australia.

Transactivating DNA-binding protein-43 (TDP-43) deposits represent a typical finding in almost all ALS patients, more than half of FTLD patients and patients with several other neurodegenerative disorders. It appears that perturbation of nucleo-cytoplasmic transport is an important event in these conditions but the mechanistic role and the fate of TDP-43 during neuronal degeneration remain elusive. We have developed an experimental system for visualising the perturbed nucleocytoplasmic transport of neuronal TDP-43 at the single-cell level in vivo using zebrafish spinal cord. Read More

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Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders.

Acta Neuropathol 2018 Jul 14;136(1):69-87. Epub 2018 Jun 14.

Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA.

Alzheimer's disease (AD) is the most common form of dementia in the elderly affecting more than 5 million people in the U.S. AD is characterized by the accumulation of β-amyloid (Aβ) and Tau in the brain, and is manifested by severe impairments in memory and cognition. Read More

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July 2018
2 Reads

Alzheimer's disease pathology propagation by exosomes containing toxic amyloid-beta oligomers.

Acta Neuropathol 2018 Jul 13;136(1):41-56. Epub 2018 Jun 13.

Department of Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

The gradual deterioration of cognitive functions in Alzheimer's disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amyloid-beta may cause propagation of pathology in a prion-like manner, although the underlying mechanisms are incompletely understood. Here we show that small extracellular vesicles, exosomes, from Alzheimer patients' brains contain increased levels of amyloid-beta oligomers and can act as vehicles for the neuron-to-neuron transfer of such toxic species in recipient neurons in culture. Read More

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July 2018
2 Reads

Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype.

Acta Neuropathol 2018 Jun 20. Epub 2018 Jun 20.

Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlapping clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to elucidate whether transactive response DNA-binding protein of 43 kDa (TDP-43) pathology contributes to clinicopathologic heterogeneity of CBD. Paraffin-embedded sections of the midbrain, pons, subthalamic nucleus, and basal forebrain from 187 autopsy-confirmed CBD cases were screened with immunohistochemistry for phospho-TDP-43. Read More

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June 2018
2 Reads

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models.

Acta Neuropathol 2018 Jun 9. Epub 2018 Jun 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

Alpha-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 mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. Read More

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Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.

Acta Neuropathol 2018 Jun 18. Epub 2018 Jun 18.

Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.

The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Read More

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June 2018
2 Reads

Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas.

Acta Neuropathol 2018 Jun 16. Epub 2018 Jun 16.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Read More

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Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Acta Neuropathol 2018 Jun 7. Epub 2018 Jun 7.

Department of Neurosciences, University of California at San Diego, La Jolla, San Diego, USA.

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Read More

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Primary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations.

Acta Neuropathol 2018 Jun 7. Epub 2018 Jun 7.

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

Patients with DICER1 predisposition syndrome have an increased risk to develop pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, and several other rare tumor entities. In this study, we identified 22 primary intracranial sarcomas, including 18 in pediatric patients, with a distinct methylation signature detected by array-based DNA-methylation profiling. In addition, two uterine rhabdomyosarcomas sharing identical features were identified. Read More

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June 2018
3 Reads

Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?

Acta Neuropathol 2018 May 24. Epub 2018 May 24.

Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.

Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. Read More

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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.

Acta Neuropathol 2018 May 16. Epub 2018 May 16.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, UK.

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, between APP 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 vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Read More

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May 2018
2 Reads

Novel FGFR2-INA fusion identified in two low-grade mixed neuronal-glial tumors drives oncogenesis via MAPK and PI3K/mTOR pathway activation.

Acta Neuropathol 2018 May 16. Epub 2018 May 16.

Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA.

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Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features.

Acta Neuropathol 2018 May 15. Epub 2018 May 15.

Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120, Heidelberg, Germany.

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Read More

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May 2018
4 Reads

K27/G34 versus K28/G35 in histone H3-mutant gliomas: A note of caution.

Acta Neuropathol 2018 May 15. Epub 2018 May 15.

Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.

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Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways.

Acta Neuropathol 2018 May 12. Epub 2018 May 12.

Faculty of Medicine, University of Southampton, Southampton, UK.

Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. Read More

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Collagen VI is required for the structural and functional integrity of the neuromuscular junction.

Acta Neuropathol 2018 May 11. Epub 2018 May 11.

Department of Molecular Medicine, University of Padova, Via Ugo Bassi 58/B, 35131, Padua, Italy.

The synaptic cleft of the neuromuscular junction (NMJ) consists of a highly specialized extracellular matrix (ECM) involved in synapse maturation, in the juxtaposition of pre- to post-synaptic areas, and in ensuring proper synaptic transmission. Key components of synaptic ECM, such as collagen IV, perlecan and biglycan, are binding partners of one of the most abundant ECM protein of skeletal muscle, collagen VI (ColVI), previously never linked to NMJ. Here, we demonstrate that ColVI is itself a component of this specialized ECM and that it is required for the structural and functional integrity of NMJs. Read More

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May 2018
2 Reads

Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer's disease and PART.

Acta Neuropathol 2018 May 11. Epub 2018 May 11.

Center for Alzheimer's and Neurodegenerative Diseases, NL10.120, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75390, USA.

Alzheimer's disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological "seeds" may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/EC). Read More

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Aging alters the immunological response to ischemic stroke.

Acta Neuropathol 2018 May 11. Epub 2018 May 11.

Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77370, USA.

The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Read More

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May 2018
1 Read

Gadolinium-based contrast agents induce gadolinium deposits in cerebral vessel walls, while the neuropil is not affected: an autopsy study.

Acta Neuropathol 2018 Jul 10;136(1):127-138. Epub 2018 May 10.

Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstraße 30, 48149, Münster, Germany.

Recent studies showed gadolinium depositions following serial administrations of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging examinations in various parts of the brain with the dentate nucleus (DN) being most affected. Even though no clinical correlates of the deposits are known yet, an intensive debate developed if this might be harmful. The aim of the current study was to specify the gadolinium distribution in brain tissue of patients who received serial injections of GBCAs in the low-µm range and to explore any potential pathological tissue changes caused by gadolinium deposits. Read More

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July 2018
10.76 Impact Factor

The lysosomal function of progranulin, a guardian against neurodegeneration.

Acta Neuropathol 2018 May 9. Epub 2018 May 9.

Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.

Progranulin (PGRN), encoded by the GRN gene in humans, is a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing and tumorigenesis. The clinical importance of PGRN became especially evident in 2006, when heterozygous mutations in the GRN gene, resulting in haploinsufficiency, were found to be one of the main causes of frontotemporal lobar degeneration (FTLD). FTLD is a clinically heterogenous disease that results in the progressive atrophy of the frontal and temporal lobes of the brain. Read More

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DNA methylation-based reclassification of olfactory neuroblastoma.

Acta Neuropathol 2018 May 5. Epub 2018 May 5.

Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. Read More

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May 2018
3 Reads

CADASIL brain vessels show a HTRA1 loss-of-function profile.

Acta Neuropathol 2018 Jul 3;136(1):111-125. Epub 2018 May 3.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 17, 81377, Munich, Germany.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and a phenotypically similar recessive condition (CARASIL) have emerged as important genetic model diseases for studying the molecular pathomechanisms of cerebral small vessel disease (SVD). CADASIL, the most frequent and intensely explored monogenic SVD, is characterized by a severe pathology in the cerebral vasculature including the mutation-induced aggregation of the Notch3 extracellular domain (Notch3) and the formation of protein deposits of insufficiently determined composition in vessel walls. To identify key molecules and pathways involved in this process, we quantitatively determined the brain vessel proteome from CADASIL patient and control autopsy samples (n = 6 for each group), obtaining 95 proteins with significantly increased abundance. Read More

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July 2018
2 Reads

Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients.

Acta Neuropathol 2018 May 3. Epub 2018 May 3.

Department of Neurology, Duke University School of Medicine, Durham, USA.

Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, early-onset, autosomal dominant form of ALS, characterized by slow disease progression and sparing of respiratory musculature. Dominant, gain-of-function mutations in the senataxin gene (SETX) cause ALS4, but the mechanistic basis for motor neuron toxicity is unknown. SETX is a RNA-binding protein with a highly conserved helicase domain, but does not possess a low-complexity domain, making it unique among ALS-linked disease proteins. Read More

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May 2018
2 Reads

Somatic mutations in neurons during aging and neurodegeneration.

Acta Neuropathol 2018 Jun 28;135(6):811-826. Epub 2018 Apr 28.

Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER, Maastricht, The Netherlands.

The nervous system is composed of a large variety of neurons with a diverse array of morphological and functional properties. This heterogeneity is essential for the construction and maintenance of a distinct set of neural networks with unique characteristics. Accumulating evidence now indicates that neurons do not only differ at a functional level, but also at the genomic level. Read More

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Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology.

Acta Neuropathol 2018 Apr 26. Epub 2018 Apr 26.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.

Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. Read More

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April 2018
1 Read

Evidence for altered dendritic spine compartmentalization in Alzheimer's disease and functional effects in a mouse model.

Acta Neuropathol 2018 Jun 25;135(6):839-854. Epub 2018 Apr 25.

Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.

Alzheimer's disease (AD) is associated with a progressive loss of synapses and neurons. Studies in animal models indicate that morphological alterations of dendritic spines precede synapse loss, increasing the proportion of large and short ("stubby") spines. Whether similar alterations occur in human patients, and what their functional consequences could be, is not known. Read More

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June 2018
2 Reads

Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.

Acta Neuropathol 2018 Jul 23;136(1):153-166. Epub 2018 Apr 23.

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AII), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIII), and WHO grade IV glioblastoma, IDH-mutant (GBM). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AII and AAIII have lost their significance. Read More

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July 2018
5 Reads

Diffusible, highly bioactive oligomers represent a critical minority of soluble Aβ in Alzheimer's disease brain.

Acta Neuropathol 2018 Jul 23;136(1):19-40. Epub 2018 Apr 23.

Laboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Building for Transformative Medicine, 60 Fenwood Road, Boston, MA, 02115, USA.

Significant data suggest that soluble Aβ oligomers play an important role in Alzheimer's disease (AD), but there is great confusion over what exactly constitutes an Aβ oligomer and which oligomers are toxic. Most studies have utilized synthetic Aβ peptides, but the relevance of these test tube experiments to the conditions that prevail in AD is uncertain. A few groups have studied Aβ extracted from human brain, but they employed vigorous tissue homogenization which is likely to release insoluble Aβ that was sequestered in plaques during life. Read More

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July 2018
1 Read

Infectious prions do not induce Aβ deposition in an in vivo seeding model.

Acta Neuropathol 2018 Jun 16;135(6):965-967. Epub 2018 Apr 16.

German Center for Neurodegenerative Diseases (DZNE), Tübingen, 72076, Tübingen, Germany.

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June 2018
1 Read

Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas.

Acta Neuropathol 2018 Jun 11;135(6):939-953. Epub 2018 Apr 11.

Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, 03080, Republic of Korea.

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. Read More

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June 2018
4 Reads

Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence.

Acta Neuropathol 2018 Jun 7;135(6):955-963. Epub 2018 Apr 7.

Department of Neuropathology, University Hospital Heidelberg, 69120, Heidelberg, Germany.

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. Read More

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June 2018
3 Reads

Reconstructing the molecular life history of gliomas.

Acta Neuropathol 2018 May 3;135(5):649-670. Epub 2018 Apr 3.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06030, USA.

At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements. Somatic abnormalities may have functional consequences, such as a decrease, increase or change in mRNA transcripts, and cells pay a penalty for maintaining them. These abnormalities, therefore, must provide cells with a competitive advantage to become engrained into the glioma genome. Read More

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May 2018
4 Reads

Mutations in LRRK2 amplify cell-to-cell protein aggregate propagation: a hypothesis.

Authors:
Patrick A Lewis

Acta Neuropathol 2018 Jun 29;135(6):973-976. Epub 2018 Mar 29.

School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, UK.

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June 2018
1 Read

An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer's disease.

Acta Neuropathol 2018 Jun 27;135(6):827-837. Epub 2018 Mar 27.

Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, University of Antwerp-CDE, Universiteitsplein 1, 2610, Antwerp, Belgium.

Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). Read More

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June 2018
1 Read

Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline.

Acta Neuropathol 2018 May 24;135(5):681-694. Epub 2018 Mar 24.

Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany.

Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. Read More

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May 2018
1 Read

Molecular characterization of medulloblastomas with extensive nodularity (MBEN).

Acta Neuropathol 2018 Mar 22. Epub 2018 Mar 22.

Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.

Medulloblastoma with extensive nodularity (MBEN) is a rare histological variant of medulloblastoma (MB). These tumors are usually occurring in the first 3 years of life and are associated with good prognosis. Molecular analyses of MBEN, mostly limited to single cases or small series, have shown that they always classify as sonic hedgehog (SHH)-driven MB. Read More

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March 2018
4 Reads

Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations.

Acta Neuropathol 2018 Mar 21. Epub 2018 Mar 21.

Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. Read More

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March 2018
13 Reads

The natural HLA ligandome of glioblastoma stem-like cells: antigen discovery for T cell-based immunotherapy.

Acta Neuropathol 2018 Jun 20;135(6):923-938. Epub 2018 Mar 20.

Laboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.

Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Read More

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June 2018
4 Reads

Energy metabolism in ALS: an underappreciated opportunity?

Acta Neuropathol 2018 Apr 16;135(4):489-509. Epub 2018 Mar 16.

Department of Neurosciences, Experimental Neurology, KU Leuven-University of Leuven, Campus Gasthuisberg O&N 4, Herestraat 49, PB 602, 3000, Leuven, Belgium.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative disorder that primarily affects motor neurons. Despite our increased understanding of the genetic factors contributing to ALS, no effective treatment is available. A growing body of evidence shows disturbances in energy metabolism in ALS. Read More

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April 2018
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Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.

Acta Neuropathol 2018 May 14;135(5):757-777. Epub 2018 Mar 14.

Developmental Biology and Cancer Programme, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. Read More

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May 2018
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