Erratum to: Time course of phosphorylated-tau181 in blood across the Alzheimer ’s disease spectrum
Alexis Moscoso, Michel J. Grothe, Nicholas J. Ashton, Thomas K. Karikari, Juan Lantero Rodriguez, Anniina Snellman, Marc Su árez-Calvet, Henrik Zetterberg, Kaj Blennow, Michael Schöll, for the Alzheimer’s Disease Neuroimaging Initiative. Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum.Brain 2021;144(1):325 –339. doi:10.1093/brain/awaa399 (Source: Brain)
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
Surface-in pathology in multiple sclerosis: a new view on pathogenesis?
AbstractWhile multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicatedin vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats
AbstractNeuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson ’s disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk fact or for Parkinson’s disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pat...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer ’s disease pathologies
AbstractAmyloid- β precursor protein (APP) is sequentially cleaved by secretases and generates amyloid-β, the major components in senile plaques in Alzheimer’s disease. APP is upregulated in human Alzheimer’s disease brains. However, the molecular mechanism of how APP contributes to Alzheimer’s disease patho genesis remains incompletely understood. Here we show that truncated APP C586-695 fragment generated by δ-secretase directly binds to CCAAT/enhancer-binding protein beta (CEBPB), an inflammatory transcription factor, and enhances its transcriptional activity, escalating Alzheimer’s disease-relate d gene expr...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
Disruption of the blood –brain barrier in 22q11.2 deletion syndrome
AbstractNeuroimmune dysregulation is implicated in neuropsychiatric disorders including schizophrenia. As the blood −brain barrier is the immunological interface between the brain and the periphery, we investigated whether this vascular phenotype is intrinsically compromised in the most common genetic risk factor for schizophrenia, the 22q11.2 deletion syndrome (22qDS). Blood−brain barrier like endothelium di fferentiated from human 22qDS+schizophrenia-induced pluripotent stem cells exhibited impaired barrier integrity, a phenotype substantiated in a mouse model of 22qDS. The proinflammatory intercellular adhesion mole...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation
AbstractParkinson ’s disease is characterized by the progressive degeneration of dopaminergic neurons within the substantia nigra pars compacta and the presence of protein aggregates in surviving neurons. The LRRK2 G2019S mutation is one of the major determinants of familial Parkinson’s disease cases and leads to late-onset Parkinson’s disease with pleomorphic pathology, including α-synuclein accumulation and deposition of protein inclusions. We demonstrated that LRRK2 phosphorylatesN-ethylmaleimide sensitive factor (NSF). We observed aggregates containing NSF in basal ganglia specimens from patients with Parkinson ...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
Impaired cerebral microcirculation in isolated REM sleep behaviour disorder
AbstractDuring the prodromal period of Parkinson ’s disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of m ood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whether pati...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy
In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but r eactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA. (Source: Brain)
Source: Brain - April 20, 2021 Category: Neurology Source Type: research
HOPS-associated neurological disorders (HOPSANDs): linking endolysosomal dysfunction to the pathogenesis of dystonia
AbstractThe homotypic fusion and protein sorting (HOPS) complex is the structural bridge necessary for the fusion of late endosomes and autophagosomes with lysosomes.Recent publications linked mutations in genes encoding HOPS complex proteins with the aetiopathogenesis of inherited dystonias (i.e.VPS16,VPS41, andVPS11). Functional and microstructural studies conducted on patient-derived fibroblasts carrying mutations of HOPS complex subunits displayed clear abnormalities of the lysosomal and autophagic compartments.We propose to name this group of diseases HOPS-associated neurological disorders (HOPSANDs), which are mainly...
Source: Brain - April 19, 2021 Category: Neurology Source Type: research
A serum microRNA sequence reveals fragile X protein pathology in amyotrophic lateral sclerosis
AbstractKnowledge about converging disease mechanisms in the heterogeneous syndrome amyotrophic lateral sclerosis (ALS) is rare, but may lead to therapies effective in most ALS cases. Previously, we identified serum microRNAs downregulated in familial ALS, the majority of sporadic ALS patients, but also in presymptomatic mutation carriers. A 5-nucleotide sequence motif (GDCGG; D = G, A or U) was strongly enriched in these ALS-related microRNAs. We hypothesized that deregulation of protein(s) binding predominantly to this consensus motif was responsible for the ALS-linked microRNA fingerprint. Using microRNA pull-down ...
Source: Brain - April 19, 2021 Category: Neurology Source Type: research
Time for N-of-1 trials in clinical decision-making
Heresy comes in many guises. Sometimes it is spoken softly, wrapped in comforting tones, persuasive despite its wicked subversion. On other occasions, it is delivered with naked provocation, a loud appeal to the rebels. Rarely, it is barely discernible, threaded deftly into an argument which, only on reflection, reveals its shocking, true intent. This one is offered in plain sight: it is time to question the orthodoxy of the way we conduct clinical trials. (Source: Brain)
Source: Brain - April 19, 2021 Category: Neurology Source Type: research
A neurogenetic analysis of female autism
AbstractFemales versus males are less frequently diagnosed with autism spectrum disorder (ASD), and while understanding sex differences is critical to delineating the systems biology of the condition, female ASD is understudied. We integrated functional MRI and genetic data in a sex-balanced sample of ASD and typically developing youth (8 –17 years old) to characterize female-specific pathways of ASD risk. Our primary objectives were to: (i) characterize female ASD (n = 45) brain response to human motion, relative to matched typically developing female youth (n = 45); and (ii) evaluate whether genetic data coul...
Source: Brain - April 16, 2021 Category: Neurology Source Type: research
Visual agnosia and imagery after Lissauer
This year marks the 130th anniversary of the untimely death of Heinrich Lissauer (1861 –91). Paolo Bartolomeo explores how the anatomical account of dissociations between perception and imagery deficits proposed by Lissauer in his 1890 article on visual agnosia, resonates with the present debate on the neural bases of visual mental imagery. (Source: Brain)
Source: Brain - April 15, 2021 Category: Neurology Source Type: research
The role of gut dysbiosis in Parkinson ’s disease: mechanistic insights and therapeutic options
AbstractParkinson ’s disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson’s disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition m ay be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson’s disease by regulating neuroinflammation, barrier function and neurot ransmitter...
Source: Brain - April 15, 2021 Category: Neurology Source Type: research
Tumour immune landscape of paediatric high-grade gliomas
AbstractOver the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations.Despite these advances, clinical trials for children with gliomas have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences be...
Source: Brain - April 15, 2021 Category: Neurology Source Type: research
