Brain communications最新文献

{"title":"Functional and connectivity correlates associated with Parkinson's disease psychosis: a systematic review.","authors":"Sara Pisani, Brandon Gunasekera, Yining Lu, Miriam Vignando, Dominic Ffytche, Dag Aarsland, K R Chaudhuri, Clive Ballard, Jee-Young Lee, Yu Kyeong Kim, Latha Velayudhan, Sagnik Bhattacharyya","doi":"10.1093/braincomms/fcae358","DOIUrl":"10.1093/braincomms/fcae358","url":null,"abstract":"<p><p>Neural underpinnings of Parkinson's disease psychosis remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here, we aimed to qualitatively synthesize evidence from studies investigating Parkinson's psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for functional MRI (task-based and resting state), diffusion tensor imaging, PET and single-photon emission computed tomography studies comparing Parkinson's disease psychosis patients with Parkinson's patients without psychosis. We report findings from 29 studies (514 Parkinson's psychosis patients, mean age ± SD = 67.92 ± 4.37 years; 51.36% males; 853 Parkinson's patients, mean age ± SD = 66.75 ± 4.19 years; 55.81% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state functional MRI studies in Parkinson's psychosis patients compared with Parkinson's patients without psychosis. Similarly, white matter abnormalities were reported in parietal, temporal and occipital regions. Hypo-metabolism and reduced dopamine transporter binding were also reported whole brain and in sub-cortical areas. This suggests extensive alterations affecting regions involved in high-order visual processing and attentional networks.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal recessive <i>VWA1</i>-related disorder: comprehensive analysis of phenotypic variability and genetic mutations.","authors":"Sara Nagy, Alistair T Pagnamenta, Elisa Cali, Hilde M H Braakman, Juerd Wijntjes, Benno Kusters, Marc Gotkine, Orly Elpeleg, Vardiella Meiner, Jerica Lenberg, Kristen Wigby, Jennifer Friedman, Luke D Perry, Alexander M Rossor, Anna Uhrova Meszarosova, Dana Thomasova, Saiju Jacob, Mary O'Driscoll, Lenika De Simone, Dorothy K Grange, Richard Sommerville, Zahra Firoozfar, Shahryar Alavi, Mahta Mazaheri, Jevin M Parmar, Phillipa J Lamont, Veronica Pini, Anna Sarkozy, Francesco Muntoni, Gianina Ravenscroft, Eppie Jones, Declan O'Rourke, Melissa Nel, Jeannine M Heckmann, Michelle Kvalsund, Musambo M Kapapa, Somwe Wa Somwe, David R Bearden, Arman Çakar, Anne-Marie Childs, Rita Horvath, Mary M Reilly, Henry Houlden, Reza Maroofian","doi":"10.1093/braincomms/fcae377","DOIUrl":"10.1093/braincomms/fcae377","url":null,"abstract":"<p><p>A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (<i>VWA1</i>). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs. Foot drop, foot deformities and distal leg weakness followed by early proximal leg weakness are confirmed to be initial manifestations. Additionally, this study identified 11 novel <i>VWA1</i> variants, reaffirming the 10 bp insertion-induced p.Gly25ArgfsTer74 as the most prevalent disease-causing allele, with a carrier frequency of ∼1 in 441 in the UK and Western European population. Importantly, VWA1-related pathology may mimic various neuromuscular conditions, advocating for its inclusion in diverse gene panels spanning hereditary neuropathies to muscular dystrophies. The study highlights the potential of lower quality control filters in exome analysis to enhance diagnostic yield of VWA1 disease that may account for up to 1% of unexplained hereditary neuropathies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma phosphorylated-tau217 is increased in Niemann-Pick disease type C.","authors":"Fernando Gonzalez-Ortiz, Thomas K Karikari, Danielle Taylor-Te Vruchte, Dawn Shepherd, Bjørn-Eivind Kirsebom, Tormod Fladby, Frances Platt, Kaj Blennow","doi":"10.1093/braincomms/fcae375","DOIUrl":"10.1093/braincomms/fcae375","url":null,"abstract":"<p><p>Niemann-Pick disease type C and Alzheimer's disease are distinct neurodegenerative disorders that share the presence of neurofibrillary tangle pathology. In this multicentre study, we measured plasma phosphorylated-tau217 in controls (<i>n</i> = 60), Niemann-Pick disease type C (<i>n</i> = 71) and Alzheimer's disease (<i>n</i> = 30 positive for amyloid and negative for tau in CSF [A⁺T^-] and <i>n</i> = 30 positive for both [A⁺T⁺]). Annual Severity Increment Score and Lysotracker measurements were evaluated in the Niemann-Pick disease type C group to estimate the rate of progression and lysosomal enlargement, respectively. In the cross-sectional analysis, plasma phosphorylated-tau217 was increased in Niemann-Pick disease type C compared with controls (2.52 ± 1.93 versus 1.02 ± 0.34 pg/mL, respectively, <i>P</i> < 0.001) and inversely correlated with age at disease onset (<i>R</i> = -0.54, <i>P</i> < 0.001). In the longitudinal analysis, plasma phosphorylated-tau217 was associated with disease progression determined by Annual Severity Increment Score (<i>R</i> = 0.48, <i>P</i> < 0.001) and lysosomal enlargement (<i>R</i> = 0.26, <i>P</i> = 0.004). We found no differences between A⁺T^- Alzheimer's disease and Niemann-Pick disease type C (2.67 ± 1.18 versus 2.52 ± 1. 93 pg/mL, <i>P</i> = 0.31); however, A⁺T⁺ Alzheimer's disease had significantly higher levels than Niemann-Pick disease type C (3.26 ± 1.36 versus 2.52 ± 1.93 pg/mL, <i>P</i> = 0.001). Our findings suggest that plasma p-tau217 can increase in brain disorders with isolated tau pathology. Plasma p-tau217 associations with disease progression and severity make it a potential marker in Niemann-Pick disease type C.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar activity in hemi-parkinsonian rats during volitional gait and freezing.","authors":"Valerie DeAngelo, Arianna Gehan, Siya Paliwal, Katherine Ho, Justin D Hilliard, Chia-Han Chiang, Jonathan Viventi, George C McConnell","doi":"10.1093/braincomms/fcae246","DOIUrl":"10.1093/braincomms/fcae246","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-hydroxydopamine toxin-induced model is the most studied animal model of Parkinson's disease, which reproduces gait dysfunction after >68% dopamine loss in the substantia nigra pars compacta. The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and dopaminergic cell loss is not clear. In this article, we report the effects of unilateral dopamine depletion on cerebellar vermis activity using micro-electrocorticography during walking and freezing on a runway. Gait and neural activity were measured in 6-hydroxydopamine- and sham-lesioned rats aged between 4 and 5 months at 14, 21 and 28 days after infusion of 6-hydroxydopamine or control vehicle into the medial forebrain bundle (<i>n</i> = 20). Gait deficits in 6-hydroxydopamine rats were different from sham rats at 14 days (<i>P</i> < 0.05). Gait deficits in 6-hydroxydopamine rats improved at 21 and 28 days except for run speed, which decreased at 28 days (<i>P</i> = 0.018). No differences in gait deficits were observed in sham-lesioned rats at any time points. Hemi-parkinsonian rats showed hyperactivity in the cerebellar vermis at 21 days (<i>P</i> < 0.05), but not at 14 and 28 days, and the activity was reduced during freezing epochs in Lobules VIa, VIb and VIc (<i>P</i> < 0.05). These results suggest that dopaminergic cell loss causes pathological cerebellar activity at 21 days post-lesion and suggest that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28 days. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in patients with Parkinson's disease making this region a potential location for biomarker detection. Although the unilateral 6-hydroxydopamine model presents gait deficits that parallel clinical presentations of Parkinson's disease, further studies in animal models of bilateral dopamine loss are needed to understand the role of the cerebellar vermis in Parkinson's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar activity in PINK1 knockout rats during volitional gait.","authors":"Valerie DeAngelo, Justin D Hilliard, Chia-Han Chiang, Jonathan Viventi, George C McConnell","doi":"10.1093/braincomms/fcae249","DOIUrl":"10.1093/braincomms/fcae249","url":null,"abstract":"<p><p>Preclinical models of Parkinson's disease are imperative to gain insight into the neural circuits that contribute to gait dysfunction in advanced stages of the disease. A PTEN-induced putative kinase 1 knockout early-onset model of Parkinson's disease may be a useful rodent model to study the effects of neurotransmitter degeneration caused by a loss of PTEN-induced putative kinase 1 function on brain activity during volitional gait. The goal of this study was to measure changes in neural activity at the cerebellar vermis at 8 months of age. It was found that gait deficits, except run speed, were not significantly different from age-matched wild-type controls, as previously reported. PTEN-induced putative kinase 1 knockout (<i>n</i> = 4) and wild-type (<i>n</i> = 4) rats were implanted with a micro-electrocorticographic array placed over cerebellar vermis Lobules VI (a-c) and VII. Local field potential recordings were obtained during volitional gait across a runway. Power spectral analysis and coherence analysis were used to quantify network oscillatory activity in frequency bands of interest. Cerebellar vermis power was hypoactive in the beta (VIb, VIc and VII) and alpha (VII) bands at cerebellar vermis Lobules VIb, VIc and VII in PTEN-induced putative kinase 1 knockout rats compared with wild-type controls during gait (<i>P</i> < 0.05). These results suggest that gait improvement in PTEN-induced putative kinase 1 knockout rats at 8 months may be a compensatory mechanism attributed to movement corrections caused by a decreased inhibition of the alpha band of cerebellar vermis Lobule VII and beta band of Lobules VIb, VIc and VII. The PTEN-induced putative kinase 1 knockout model may be a valuable tool for understanding the circuit mechanisms underlying gait dysfunction in patients with early-onset Parkinson's disease with a functional loss of PTEN-induced putative kinase 1. Future studies investigating the cerebellar vermis as a potential biomarker and therapeutic target for the treatment of gait dysfunction in Parkinson's disease are warranted.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced MRI-based brain tumour classification with a novel Pix2pix generative adversarial network augmentation framework.","authors":"Efe Precious Onakpojeruo, Mubarak Taiwo Mustapha, Dilber Uzun Ozsahin, Ilker Ozsahin","doi":"10.1093/braincomms/fcae372","DOIUrl":"10.1093/braincomms/fcae372","url":null,"abstract":"<p><p>The scarcity of medical imaging datasets and privacy concerns pose significant challenges in artificial intelligence-based disease prediction. This poses major concerns to patient confidentiality as there are now tools capable of extracting patient information by merely analysing patient's imaging data. To address this, we propose the use of synthetic data generated by generative adversarial networks as a solution. Our study pioneers the utilisation of a novel Pix2Pix generative adversarial network model, specifically the 'image-to-image translation with conditional adversarial networks,' to generate synthetic datasets for brain tumour classification. We focus on classifying four tumour types: glioma, meningioma, pituitary and healthy. We introduce a novel conditional deep convolutional neural network architecture, developed from convolutional neural network architectures, to process the pre-processed generated synthetic datasets and the original datasets obtained from the Kaggle repository. Our evaluation metrics demonstrate the conditional deep convolutional neural network model's high performance with synthetic images, achieving an accuracy of 86%. Comparative analysis with state-of-the-art models such as Residual Network50, Visual Geometry Group 16, Visual Geometry Group 19 and InceptionV3 highlights the superior performance of our conditional deep convolutional neural network model in brain tumour detection, diagnosis and classification. Our findings underscore the efficacy of our novel Pix2Pix generative adversarial network augmentation technique in creating synthetic datasets for accurate brain tumour classification, offering a promising avenue for improved disease prediction and treatment planning.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter protection with insulin-like growth factor-1 after hypoxia-ischaemia in preterm foetal sheep.","authors":"Guido Wassink, Kenta H T Cho, Sam Mathai, Christopher A Lear, Justin M Dean, Alistair J Gunn, Laura Bennet","doi":"10.1093/braincomms/fcae373","DOIUrl":"10.1093/braincomms/fcae373","url":null,"abstract":"<p><p>Perinatal hypoxia-ischaemia in extremely preterm infants is associated with long-term neurodevelopmental impairment, for which there is no specific treatment. Insulin-like growth factor-1 can reduce acute brain injury, but its effects on chronic white matter injury after hypoxia-ischaemia are unclear. Preterm-equivalent foetal sheep (0.6 gestation) received either sham-asphyxia or asphyxia induced by umbilical cord occlusion for 30 min, and recovered for either 3 or 35 days after asphyxia. The 35 day recovery groups received either an intracerebroventricular infusion of insulin-like growth factor-1 (1 µg/24 h) or vehicle, from 3 to 14 days after asphyxia. Asphyxia was associated with ventricular enlargement, and loss of frontal and parietal white matter area (<i>P</i> < 0.05 versus sham-asphyxia). This was associated with reduced area fraction of myelin basic protein and numbers of oligodendrocyte transcription factor 2 and mature, anti-adenomatous polyposis coli-positive oligodendrocytes in periventricular white matter (<i>P</i> < 0.05), with persistent inflammation and caspase-3 activation (<i>P</i> < 0.05). Four of eight foetuses developed cystic lesions in temporal white matter. Prolonged infusion with insulin-like growth factor-1 restored frontal white matter area, improved numbers of oligodendrocyte transcription factor 2-positive and mature, anti-adenomatous polyposis coli-positive oligodendrocytes, with reduced astrogliosis and microgliosis after 35 days recovery (<i>P</i> < 0.05 versus asphyxia). One of four foetuses developed temporal cystic lesions. Functionally, insulin-like growth factor-1-treated foetuses had faster recovery of EEG power, but not spectral edge. Encouragingly, these findings show that delayed, prolonged, insulin-like growth factor-1 treatment can improve functional maturation of periventricular white matter after severe asphyxia in the very immature brain, at least in part by suppressing chronic neural inflammation.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spine-brain axis: is spinal anatomy associated with brain volume?","authors":"Sergio Grosu, Trayana Nikolova, Roberto Lorbeer, Veit M Stoecklein, Susanne Rospleszcz, Nicola Fink, Christopher L Schlett, Corinna Storz, Ebba Beller, Daniel Keeser, Margit Heier, Lena S Kiefer, Elke Maurer, Sven S Walter, Birgit B Ertl-Wagner, Jens Ricke, Fabian Bamberg, Annette Peters, Sophia Stoecklein","doi":"10.1093/braincomms/fcae365","DOIUrl":"10.1093/braincomms/fcae365","url":null,"abstract":"<p><p>First small sample studies indicate that disturbances of spinal morphology may impair craniospinal flow of cerebrospinal fluid and result in neurodegeneration. The aim of this study was to evaluate the association of cervical spinal canal width and scoliosis with grey matter, white matter, ventricular and white matter hyperintensity volumes of the brain in a large study sample. Four hundred participants underwent whole-body 3 T magnetic resonance imaging. Grey matter, white matter and ventricular volumes were quantified using a warp-based automated brain volumetric approach. Spinal canal diameters were measured manually at the cervical vertebrae 2/3 level. Scoliosis was evaluated using manual measurements of the Cobb angle. Linear binomial regression analyses of measures of brain volumes and spine anatomy were performed while adjusting for age, sex, hypertension, cholesterol levels, body mass index, smoking and alcohol consumption. Three hundred eighty-three participants were included [57% male; age: 56.3 (±9.2) years]. After adjustment, smaller spinal canal width at the cervical vertebrae 2/3 level was associated with lower grey matter (<i>P</i> = 0.034), lower white matter (<i>P</i> = 0.012) and higher ventricular (<i>P</i> = 0.006, inverse association) volume. Participants with scoliosis had lower grey matter (<i>P</i> = 0.005), lower white matter (<i>P</i> = 0.011) and larger brain ventricular (<i>P</i> = 0.003) volumes than participants without scoliosis. However, these associations were attenuated after adjustment. Spinal canal width at the cervical vertebrae 2/3 level and scoliosis were not associated with white matter hyperintensity volume before and after adjustment (<i>P</i> > 0.864). In our study, cohort smaller spinal canal width at the cervical vertebrae 2/3 level and scoliosis were associated with lower grey and white matter volumes and larger ventricle size. These characteristics of the spine might constitute independent risk factors for neurodegeneration.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A glycan biomarker predicts cognitive decline in amyloid- and tau-negative patients.","authors":"Robin Ziyue Zhou, Frida Duell, Michael Axenhus, Linus Jönsson, Bengt Winblad, Lars O Tjernberg, Sophia Schedin-Weiss","doi":"10.1093/braincomms/fcae371","DOIUrl":"10.1093/braincomms/fcae371","url":null,"abstract":"<p><p>Early detection of Alzheimer's disease is vital for timely treatment. Existing biomarkers for Alzheimer's disease reflect amyloid- and tau-related pathology, but it is unknown whether the disease can be detected before cerebral amyloidosis is observed. N-glycosylation has been suggested as an upstream regulator of both amyloid and tau pathology, and levels of the N-glycan structure bisecting N-acetylglucosamine (GlcNAc) correlate with tau in blood and CSF already at pre-clinical stages of the disease. Therefore, we aimed to evaluate whether bisecting GlcNAc could predict future cognitive decline in patients from a memory clinic cohort, stratified by amyloid/tau status. We included 251 patients (mean age: 65.6 ± 10.6 years, 60.6% female) in the GEDOC cohort, from the Memory Clinic at Karolinska University Hospital, Stockholm, Sweden. Patients were classified as amyloid/tau positive or negative based on CSF biomarkers. Cognitive decline, measured by longitudinal Mini-Mental State Examination scores, was followed for an average of 10.7 ± 4.1 years and modelled using non-linear mixed effects models. Additionally, bisecting GlcNAc levels were measured in hippocampus and cortex with lectin-based immunohistochemistry in 10 Alzheimer's disease and control brains. We found that CSF bisecting GlcNAc levels were elevated in tau-positive individuals compared with tau-negative individuals, but not in amyloid-positive individuals compared with amyloid-negative individuals. In the whole sample, high levels of CSF bisecting GlcNAc predicted earlier cognitive decline. Strikingly, amyloid/tau stratification showed that high CSF bisecting GlcNAc levels predicted earlier cognitive decline in amyloid-negative patients (<i>β</i> = 2.53 ± 0.85 years, <i>P</i> = 0.003) and tau-negative patients (<i>β</i> = 2.43 ± 1.01 years, <i>P</i> = 0.017), but not in amyloid- or tau-positive patients. Finally, histochemical analysis of bisecting GlcNAc showed increased levels in neurons in hippocampus and cortex of Alzheimer's disease compared with control brain (fold change = 1.44-1.49, <i>P</i> < 0.001). In conclusion, high CSF levels of bisecting GlcNAc reflected neuronal pathology and predicted cognitive decline in amyloid- and tau-negative individuals, suggesting that abnormal glycosylation precedes cerebral amyloidosis and tau hyper-phosphorylation in Alzheimer's disease. Bisecting GlcNAc is a promising novel early biomarker for Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations and challenges in predicting cognitive trajectories after stroke.","authors":"Nele Demeyere, Margaret J Moore","doi":"10.1093/braincomms/fcae364","DOIUrl":"10.1093/braincomms/fcae364","url":null,"abstract":"<p><p>This scientific commentary refers to 'Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms', by Matsulevits <i>et al</i>. (https://doi.org/10.1093/braincomms/fcae338).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}