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

Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau
AbstractIn Alzheimer ’s disease (AD) and other tauopathies, the cytosolic protein Tau misfolds and forms intracellular aggregates which accumulate within the brain leading to neurodegeneration. Clinical progression is tightly linked to the progressive spread of Tau pathology throughout the brain, and several lines of evidence suggest that Tau aggregates or “seeds” may propagate pathology by spreading from cell to cell in a “prion like” manner. Accordingly, blocking the spread of extracellular seeds with an antibody could be a viable therapeutic approach. However, as the structure of Tau seeds ...
Source: Acta Neuropathologica - September 20, 2018 Category: Neurology Source Type: research

Picomolar concentrations of oligomeric alpha-synuclein sensitizes TLR4 to play an initiating role in Parkinson ’s disease pathogenesis
AbstractDespite the wealth of genomic and transcriptomic data in Parkinson ’s disease (PD), the initial molecular events are unknown. Using LD score regression analysis, we show significant enrichment in PD heritability within regulatory sites for LPS-activated monocytes and that TLR4 expression is highest within human substantia nigra, the most affected brain region, su ggesting a role for TLR4 inflammatory responses. We then performed extended incubation of cells with physiological concentrations of small alpha-synuclein oligomers observing the development of a TLR4-dependent sensitized inflammatory response with t...
Source: Acta Neuropathologica - September 17, 2018 Category: Neurology Source Type: research

Nodding syndrome in Uganda is a tauopathy
We report the neuropathologic findings in five fatal cases (13 –18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem. There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina. The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed gl...
Source: Acta Neuropathologica - September 15, 2018 Category: Neurology Source Type: research

Sex and age interact to determine clinicopathologic differences in Alzheimer ’s disease
AbstractWomen reportedly make up two-thirds of Alzheimer ’s disease (AD) dementia sufferers. Many estimates regarding AD, however, are based on clinical series lacking autopsy confirmation. The Florida Autopsied Multi-Ethnic (FLAME) cohort was queried for AD cases with a total of 1625 identified ranging in age from 53 to 102 years at death. Standard ne uropathologic procedures were employed and clinical information was retrospectively collected. Clinicopathologic and genetic data (MAPT andAPOE) were stratified by sex. Within the neuropathologically diagnosed AD cohort, the overall number of women and men did not...
Source: Acta Neuropathologica - September 15, 2018 Category: Neurology Source Type: research

Nodding syndrome in Uganda is a tauopathy
We report the neuropathologic findings in five fatal cases (13 –18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem. There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina. The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed gl...
Source: Acta Neuropathologica - September 15, 2018 Category: Neurology Source Type: research

The genetic landscape of gliomas arising after therapeutic radiation
AbstractRadiotherapy improves survival for common childhood cancers such as medulloblastoma, leukemia, and germ cell tumors. Unfortunately, long-term survivors suffer sequelae that can include secondary neoplasia. Gliomas are common secondary neoplasms after cranial or craniospinal radiation, most often manifesting as high-grade astrocytomas with poor clinical outcomes. Here, we performed genetic profiling on a cohort of 12 gliomas arising after therapeutic radiation to determine their molecular pathogenesis and assess for differences in genomic signature compared to their spontaneous counterparts. We identified a high fre...
Source: Acta Neuropathologica - September 8, 2018 Category: Neurology Source Type: research

Astrocytic degeneration in chronic traumatic encephalopathy
AbstractChronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated head traumas. Using immunohistochemistry for glial fibrillary acidic protein as a marker, plus automated quantitative analysis, we examined the characteristics and extent of astrogliosis present in stage III and IV CTE, along with Alzheimer ’s disease (AD), and frontotemporal dementia (FTD) cases. Astrogliosis in CTE patients was more diffuse compared to that of AD and FTD patients, which was concentrated in the sulcal depths. Of 14 patients with CTE, 10 exhibited signs of a degenerating astrocyte pathology, charact...
Source: Acta Neuropathologica - September 7, 2018 Category: Neurology Source Type: research

Opposite development of short- and long-range anterior cingulate pathways in autism
AbstractAutism has been linked with the changes in brain connectivity that disrupt neural communication, especially involving frontal networks. Pathological changes in white matter are evident in adults with autism, particularly affecting axons below the anterior cingulate cortices (ACC). It is still unknown whether axon pathology appears early or late in development and whether it changes or not from childhood through adulthood. To address these questions, we examined typical and pathological development of about 1 million axons in post-mortem brains of children, adolescents, and adults with and without autism (ages 3 &nd...
Source: Acta Neuropathologica - September 6, 2018 Category: Neurology Source Type: research

Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer ’s disease
In this study, we observed 3000 synapses and find region-specific differences in synaptic mitochondria in AD cases compared to controls. In BA41/42, we observe a fourfold reduction in the proportion of presynaptic terminals that contain multiple mitochondria profiles in AD. We also observe ultrastructural changes including abnormal mitochondrial morphology, the presence of multivesicular bodies in s ynapses, and reduced synapse apposition length near plaques in AD. Together, our data show region-specific changes in synaptic mitochondria in AD and support the idea that the transport of mitochondria to presynaptic terminals ...
Source: Acta Neuropathologica - September 6, 2018 Category: Neurology Source Type: research

Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDH wt astrocytoma to glioblastoma
AbstractEGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10 −), andTERT promoter mutation (pTERTmut) are alterations frequently observed in adultIDH-wild-type (IDHwt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgradingIDHwt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution ofEGFRamp, 7+/10 −, and pTERTmut by analyzing high-resolution copy-number profiles and next-generation sequencing data of primary brain tumors. ...
Source: Acta Neuropathologica - September 5, 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 - August 24, 2018 Category: Neurology Source Type: research

Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease
AbstractThe deposition of pathologic misfolded proteins in neurodegenerative disorders such as Alzheimer ’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis is hypothesized to burden protein homeostatic (proteostatic) machinery, potentially leading to insufficient capacity to maintain the proteome. This hypothesis has been supported by previous work in our lab oratory, as evidenced by the perturbation of cytosolic protein solubility in response to amyloid plaques in a mouse model of Alzheimer’s amyloidosis. In the current study, we demonstrate changes in proteome sol...
Source: Acta Neuropathologica - August 23, 2018 Category: Neurology Source Type: research

Divergent brain gene expression patterns associate with distinct cell-specific tau neuropathology traits in progressive supranuclear palsy
In this study, we integrated brain gene expression measurements, quantitative neuropathology traits and genome-wide genotypes from 268 autopsy-confirmed PSP patients to identify transcriptional associations with unique cell-specific tau pathologies. We provide individual transcript and transcriptional network associations for quantitative oligodendroglial (coiled bodies = CB), neuronal (neurofibrillary tangles = NFT), astrocytic (tufted astrocytes = TA) tau pathology, and tau threads and genomic annotations of these findings. We identified divergent patterns of transcriptional associations for the distinct tau lesions, wit...
Source: Acta Neuropathologica - August 22, 2018 Category: Neurology Source Type: research

“Minimal change” multiple system atrophy with limbic-predominant α-synuclein pathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 20, 2018 Category: Neurology Source Type: research

DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome
AbstractProgressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associatedDMD gene a...
Source: Acta Neuropathologica - August 19, 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 - August 19, 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 - August 16, 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 - August 10, 2018 Category: Neurology Source Type: research

Correction to: DNA methylation-based reclassification of olfactory neuroblastoma
In the original publication, the second name of the twentieth author was incorrect. It should read as ‘Miguel Sáinz-Jaspeado’. The original publication of the article has been updated to reflect the change. This correction was authored by Ulrich Schüller on behalf of all authors of the original publication. (Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 9, 2018 Category: Neurology Source Type: research

Different patterns of hippocampal tau pathology in Alzheimer ’s disease and PART
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - August 7, 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 - August 3, 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 - July 25, 2018 Category: Neurology Source Type: research

On the origin of tau seeding activity in Alzheimer ’s disease
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 23, 2018 Category: Neurology Source Type: research

HEIRECA! The HEIdelberg REvolution of CAncer classification and what it means for neurooncology and neuropathology
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - July 20, 2018 Category: Neurology Source Type: research