Brain communicationsPub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae338
Anna Matsulevits, Pierrick Coupé, Huy-Dung Nguyen, Lia Talozzi, Chris Foulon, Parashkev Nachev, Maurizio Corbetta, Thomas Tourdias, Michel Thiebaut de Schotten
{"title":"Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms.","authors":"Anna Matsulevits, Pierrick Coupé, Huy-Dung Nguyen, Lia Talozzi, Chris Foulon, Parashkev Nachev, Maurizio Corbetta, Thomas Tourdias, Michel Thiebaut de Schotten","doi":"10.1093/braincomms/fcae338","DOIUrl":"10.1093/braincomms/fcae338","url":null,"abstract":"<p><p>This study investigates the efficacy of deep-learning models in expediting the generation of disconnectomes for individualized prediction of neuropsychological outcomes one year after stroke. Utilising a 3D U-Net network, we trained a model on a dataset of <i>N</i> = 1333 synthetic lesions and corresponding disconnectomes, subsequently applying it to <i>N</i> = 1333 real stroke lesions. The model-generated disconnection patterns were then projected into a two-dimensional 'morphospace' via uniform manifold approximation and projection for dimension reduction dimensionality reduction. We correlated the positioning within this morphospace with one-year neuropsychological scores across 86 metrics in a novel cohort of 119 stroke patients, employing multiple regression models and validating the findings in an out-of-sample group of 20 patients. Our results demonstrate that the 3D U-Net model captures the critical information of conventional disconnectomes with a notable increase in efficiency, generating deep-disconnectomes 720 times faster than current state-of-the-art software. The predictive accuracy of neuropsychological outcomes by deep-disconnectomes averaged 85.2% (<i>R</i> <sup>2</sup> = 0.208), which significantly surpassed the conventional disconnectome approach (<i>P</i> = 0.009). These findings mark a substantial advancement in the production of disconnectome maps via deep learning, suggesting that this method could greatly enhance the prognostic assessment and clinical management of stroke survivors by incorporating disconnection patterns as a predictive tool.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514649","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}
Brain communicationsPub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae341
Simona Garobbio, Reza Mazloum, Michael Rosio, Jeanette Popovova, Raphaela Schöpfer, Fabienne C Fierz, Leah R Disse, Konrad Peter Weber, Christoph J Schankin, Lars Michels, Michael H Herzog
{"title":"Understanding visual perception in visual snow syndrome: a battery of psychophysical tests plus the 30-day clinical diary.","authors":"Simona Garobbio, Reza Mazloum, Michael Rosio, Jeanette Popovova, Raphaela Schöpfer, Fabienne C Fierz, Leah R Disse, Konrad Peter Weber, Christoph J Schankin, Lars Michels, Michael H Herzog","doi":"10.1093/braincomms/fcae341","DOIUrl":"https://doi.org/10.1093/braincomms/fcae341","url":null,"abstract":"<p><p>Patients with visual snow syndrome (VSS) experience uncountable flickering tiny dots in the entire visual field. Symptoms often persist over the years. Very little is known about altered perception in VSS. VSS is diagnosed based on subjective reports because there is no manual with objective measures. In this study, 20 patients with VSS and 17 healthy controls performed a battery of tests assessing visual acuity, contrast sensitivity, illusion perception, spatial-temporal vision, motion perception, visual attention, and selective attention. Surprisingly, except for one test, which is the honeycomb illusion, patients performed at the same level as controls. Patients reporting black and white visual snow performed better in the Stroop test compared to patients reporting other visual snow colours. In addition to a clinical visit, the 30-day clinical diary was administered to patients to broadly measure their symptom severity. We found that better performance in the tests, in particular in the contrast and coherent motion tests, was correlated with lower VSS symptoms, weaker VS characteristics (e.g. density and size) and lower VS severity. Our results suggest that, even if visual abilities are not deteriorated by VSS, they can determine how severe symptoms are, and show that VSS is an heterogenous disorder where symptoms and visual abilities vary between patients, for instance depending on the VS colour. The study was primarily designed to identify tests where performance differs between controls and patients. In addition, exploratory analyses were conducted to initiate an understanding of the overall pattern of relationships between patients' visual abilities and symptoms, which is of clinical relevance. Future studies with more power are necessary to validate our findings.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483049","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}
Brain communicationsPub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae335
Mark J Cook
{"title":"From seizure to stability: unveiling the brain's network changes with anti-seizure medication.","authors":"Mark J Cook","doi":"10.1093/braincomms/fcae335","DOIUrl":"https://doi.org/10.1093/braincomms/fcae335","url":null,"abstract":"<p><p>This scientific commentary refers to 'Brain network changes after the first seizure: an insight into medication response?', by Pedersen <i>et al</i>. (https://doi.org/10.1093/braincomms/fcae328).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516812","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}
Brain communicationsPub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae320
Ryan S Gallagher, Nishant Sinha, Akash R Pattnaik, William K S Ojemann, Alfredo Lucas, Joshua J LaRocque, John M Bernabei, Adam S Greenblatt, Elizabeth M Sweeney, Iahn Cajigas, H Isaac Chen, Kathryn A Davis, Erin C Conrad, Brian Litt
{"title":"The sixth sense: how much does interictal intracranial EEG add to determining the focality of epileptic networks?","authors":"Ryan S Gallagher, Nishant Sinha, Akash R Pattnaik, William K S Ojemann, Alfredo Lucas, Joshua J LaRocque, John M Bernabei, Adam S Greenblatt, Elizabeth M Sweeney, Iahn Cajigas, H Isaac Chen, Kathryn A Davis, Erin C Conrad, Brian Litt","doi":"10.1093/braincomms/fcae320","DOIUrl":"https://doi.org/10.1093/braincomms/fcae320","url":null,"abstract":"<p><p>Intracranial EEG is used for two main purposes: to determine (i) if epileptic networks are amenable to focal treatment and (ii) where to intervene. Currently, these questions are answered qualitatively and differently across centres. There is a need to quantify the focality of epileptic networks systematically, which may guide surgical decision-making, enable large-scale data analysis and facilitate multi-centre prospective clinical trials. We analysed interictal data from 101 patients with drug-resistant epilepsy who underwent pre-surgical evaluation with intracranial EEG at a single centre. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. Sixty-five patients had unifocal seizure onset on intracranial EEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal intracranial EEG abnormalities for each patient. We compared these measures against the '5 Sense Score,' a pre-implant prediction of the likelihood of focal seizure onset, assessed the ability to predict unifocal seizure onset by combining these metrics and evaluated how predicted focality relates to subsequent treatment and outcomes. The spatial dispersion of intracranial EEG electrodes predicted network focality with similar performance to the 5-SENSE score [area under the receiver operating characteristic curve = 0.68 (95% confidence interval 0.57, 0.78)], indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5-SENSE score and the spatial dispersion of interictal intracranial EEG abnormalities significantly improved this prediction [area under the receiver operating characteristic curve = 0.79 (95% confidence interval 0.70, 0.88); <i>P</i> < 0.05]. Predictions from this combined model differed between surgical- from device-treated patients with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.68, 0.85) and between patients with good and poor post-surgical outcome at 2 years with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.56, 0.85). Spatial measures of interictal intracranial EEG abnormality significantly improved upon pre-implant predictions of network focality by area under the receiver operating characteristic curve and increased sensitivity in a single-centre study. Quantified focality predictions related to ultimate treatment strategy and surgical outcomes. While the 5-SENSE score weighed for specificity in their multi-centre validation to prevent unnecessary implantation, sensitivity improvement found in our single-centre study by including intracranial EEG may aid the decision on whom to perform the focal intervention. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514658","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}
Brain communicationsPub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae333
Neng-Wei Hu, Tomas Ondrejcak, Igor Klyubin, Yin Yang, Dominic M Walsh, Frederick J Livesey, Michael J Rowan
{"title":"Patient-derived tau and amyloid-β facilitate long-term depression <i>in vivo</i>: role of tumour necrosis factor-α and the integrated stress response.","authors":"Neng-Wei Hu, Tomas Ondrejcak, Igor Klyubin, Yin Yang, Dominic M Walsh, Frederick J Livesey, Michael J Rowan","doi":"10.1093/braincomms/fcae333","DOIUrl":"10.1093/braincomms/fcae333","url":null,"abstract":"<p><p>Alzheimer's disease is characterized by a progressive cognitive decline in older individuals accompanied by the deposition of two pathognomonic proteins amyloid-β and tau. It is well documented that synaptotoxic soluble amyloid-β aggregates facilitate synaptic long-term depression, a major form of synaptic weakening that correlates with cognitive status in Alzheimer's disease. Whether synaptotoxic tau, which is also associated strongly with progressive cognitive decline in patients with Alzheimer's disease and other tauopathies, also causes facilitation remains to be clarified. Young male adult and middle-aged rats were employed. Synaptotoxic tau and amyloid-β were obtained from different sources including (i) aqueous brain extracts from patients with Alzheimer's disease and Pick's disease tauopathy; (ii) the secretomes of induced pluripotent stem cell-derived neurons from individuals with trisomy of chromosome 21; and (iii) synthetic amyloid-β. <i>In vivo</i> electrophysiology was performed in urethane anaesthetized animals. Evoked field excitatory postsynaptic potentials were recorded from the stratum radiatum in the CA1 area of the hippocampus with electrical stimulation to the Schaffer collateral-commissural pathway. To study the enhancement of long-term depression, relatively weak low-frequency electrical stimulation was used to trigger peri-threshold long-term depression. Synaptotoxic forms of tau or amyloid-β were administered intracerebroventricularly. The ability of agents that inhibit the cytokine tumour necrosis factor-α or the integrated stress response to prevent the effects of amyloid-β or tau on long-term depression was assessed after local or systemic injection, respectively. We found that diffusible tau from Alzheimer's disease or Pick's disease patients' brain aqueous extracts or the secretomes of trisomy of chromosome 21 induced pluripotent stem cell-derived neurons, like Alzheimer's disease brain-derived amyloid-β and synthetic oligomeric amyloid-β, potently enhanced synaptic long-term depression in live rats. We further demonstrated that long-term depression facilitation by both tau and amyloid-β was age-dependent, being more potent in middle-aged compared with young animals. Finally, at the cellular level, we provide pharmacological evidence that tumour necrosis factor-α and the integrated stress response are downstream mediators of long-term depression facilitation by both synaptotoxic tau and amyloid-β. Overall, these findings reveal the promotion of an age-dependent synaptic weakening by both synaptotoxic tau and amyloid-β. Pharmacologically targeting shared mechanisms of tau and amyloid-β synaptotoxicity, such as tumour necrosis factor-α or the integrated stress response, provides an attractive strategy to treat early Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402330","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}
Brain communicationsPub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae334
Eileen Luders, Debra Spencer, Christian Gaser, Ajay Thankamony, Ieuan A Hughes, Umasuthan Srirangalingam, Helena Gleeson, Karson T F Kung, Ryan P Cabeen, Melissa Hines, Florian Kurth
{"title":"White matter variations in congenital adrenal hyperplasia: possible implications for glucocorticoid treatment.","authors":"Eileen Luders, Debra Spencer, Christian Gaser, Ajay Thankamony, Ieuan A Hughes, Umasuthan Srirangalingam, Helena Gleeson, Karson T F Kung, Ryan P Cabeen, Melissa Hines, Florian Kurth","doi":"10.1093/braincomms/fcae334","DOIUrl":"10.1093/braincomms/fcae334","url":null,"abstract":"<p><p>Congenital adrenal hyperplasia has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group and/or did not correct for brain size. Here, we examined the largest sample to date, comprising 53 male and female participants with congenital adrenal hyperplasia, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence. The four groups were compared with respect to their total white matter as well as white matter hyperintensities while applying brain size corrections. For both measures, total white matter and white matter hyperintensities, there were no significant sex differences or group-by-sex interactions. However, individuals with congenital adrenal hyperplasia had significantly smaller total white matter volumes compared to controls. Our findings align with previous reports of white matter variations in congenital adrenal hyperplasia. The absence of a group-by-sex interaction suggests that white matter variations in congenital adrenal hyperplasia may not be attributable to prenatal androgens. Instead, they may be a result of the condition itself and/or its treatment with glucocorticoids. The latter aspect warrants follow-up, particularly given that glucocorticoids are employed not only in congenital adrenal hyperplasia but also in other medical conditions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483050","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}
Brain communicationsPub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae332
Max J Kurz, Brittany K Taylor, Elizabeth Heinrichs-Graham, Rachel K Spooner, Sarah E Baker, Tony W Wilson
{"title":"Motor practice related changes in the sensorimotor cortices of youth with cerebral palsy.","authors":"Max J Kurz, Brittany K Taylor, Elizabeth Heinrichs-Graham, Rachel K Spooner, Sarah E Baker, Tony W Wilson","doi":"10.1093/braincomms/fcae332","DOIUrl":"10.1093/braincomms/fcae332","url":null,"abstract":"<p><p>The altered sensorimotor cortical dynamics seen in youth with cerebral palsy appear to be tightly coupled with their motor performance errors and uncharacteristic mobility. Very few investigations have used these cortical dynamics as potential biomarkers to predict the extent of the motor performance changes that might be seen after physical therapy or in the design of new therapeutic interventions that target a youth's specific neurophysiological deficits. This cohort investigation was directed at evaluating the practice dependent changes in the sensorimotor cortical oscillations exhibited by youth with cerebral palsy as a step towards addressing this gap. We used magnetoencephalography to image the changes in the cortical oscillations before and after youth with cerebral palsy (<i>N</i> = 25; age = 15.2 ± 4.5 years; Gross Motor Function Classification Score Levels I-III) and neurotypical controls (<i>N</i> = 18; age = 14.6 ± 3.1 years) practiced a knee extension isometric target-matching task. Subsequently, structural equation modelling was used to assess the multivariate relationship between changes in beta (16-22 Hz) and gamma (66-82 Hz) oscillations and the motor performance after practice. The structural equation modelling results suggested youth with cerebral palsy who had a faster reaction time after practice tended to also have a stronger peri-movement beta oscillation in the sensorimotor cortices following practicing. The stronger beta oscillations were inferred to reflect greater certainty in the selected motor plan. The models also indicated that youth with cerebral palsy who overshot the targets less and matched the targets sooner tended to have a stronger execution-related gamma response in the sensorimotor cortices after practice. This stronger gamma response may represent improve activation of the sensorimotor neural generators and/or alterations in the GABAergic interneuron inhibitory-excitatory dynamics. These novel neurophysiological results provide a window on the potential neurological changes governing the practice-related outcomes in the context of the physical therapy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402329","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}
Brain communicationsPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae330
Laura M Watts, David J Bunyan, Edoardo Giacopuzzi, Susan Walker, Gabriella Gazdagh, N Simon Thomas, Volker Straub, Anne-Marie Childs, Joan Forsyth, Julie Vogt, Shagufta Khan, Tracey A Willis, Jenny C Taylor, Alistair T Pagnamenta
{"title":"<i>FILIP1</i>-associated neuromuscular disorder and phenotypic blending due to paternal UPD6.","authors":"Laura M Watts, David J Bunyan, Edoardo Giacopuzzi, Susan Walker, Gabriella Gazdagh, N Simon Thomas, Volker Straub, Anne-Marie Childs, Joan Forsyth, Julie Vogt, Shagufta Khan, Tracey A Willis, Jenny C Taylor, Alistair T Pagnamenta","doi":"10.1093/braincomms/fcae330","DOIUrl":"10.1093/braincomms/fcae330","url":null,"abstract":"","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395939","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}
Brain communicationsPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae331
Natalie C Edwards, Patrick J Lao, Mohamad J Alshikho, Olivia M Ericsson, Batool Rizvi, Melissa E Petersen, Sid O'Bryant, Lisi Flores Aguilar, Sabrina Simoes, Mark Mapstone, Dana L Tudorascu, Shorena Janelidze, Oskar Hansson, Benjamin L Handen, Bradley T Christian, Joseph H Lee, Florence Lai, H Diana Rosas, Shahid Zaman, Ira T Lott, Michael A Yassa, José Gutierrez, Donna M Wilcock, Elizabeth Head, Adam M Brickman
{"title":"Cerebrovascular disease is associated with Alzheimer's plasma biomarker concentrations in adults with Down syndrome.","authors":"Natalie C Edwards, Patrick J Lao, Mohamad J Alshikho, Olivia M Ericsson, Batool Rizvi, Melissa E Petersen, Sid O'Bryant, Lisi Flores Aguilar, Sabrina Simoes, Mark Mapstone, Dana L Tudorascu, Shorena Janelidze, Oskar Hansson, Benjamin L Handen, Bradley T Christian, Joseph H Lee, Florence Lai, H Diana Rosas, Shahid Zaman, Ira T Lott, Michael A Yassa, José Gutierrez, Donna M Wilcock, Elizabeth Head, Adam M Brickman","doi":"10.1093/braincomms/fcae331","DOIUrl":"10.1093/braincomms/fcae331","url":null,"abstract":"<p><p>By age 40 years, over 90% of adults with Down syndrome have Alzheimer's disease pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with Down syndrome have elevated cerebrovascular disease markers that track with the clinical progression of Alzheimer's disease, suggesting a role of cerebrovascular disease that is hypothesized to be mediated by inflammatory factors. This study examined the pathways through which small vessel cerebrovascular disease contributes to Alzheimer's disease-related pathophysiology and neurodegeneration in adults with Down syndrome. One hundred eighty-five participants from the Alzheimer's Biomarkers Consortium-Down Syndrome [mean (SD) age = 45.2 (9.3) years] with available MRI and plasma biomarker data were included in this study. White matter hyperintensity (WMH) volumes were derived from T2-weighted fluid-attenuated inversion recovery MRI scans, and plasma biomarker concentrations of amyloid beta 42/40, phosphorylated tau 217, astrocytosis (glial fibrillary acidic protein) and neurodegeneration (neurofilament light chain) were measured with ultrasensitive immunoassays. We examined the bivariate relationships of WMH, amyloid beta 42/40, phosphorylated tau 217 and glial fibrillary acidic protein with age-residualized neurofilament light chain across Alzheimer's disease diagnostic groups. A series of mediation and path analyses examined statistical pathways linking WMH and Alzheimer's disease pathophysiology to promote neurodegeneration in the total sample and groups stratified by clinical diagnosis. There was a direct and indirect bidirectional effect through the glial fibrillary acidic protein of WMH on phosphorylated tau 217 concentration, which was associated with neurofilament light chain concentration in the entire sample. Amongst cognitively stable participants, WMH was directly and indirectly, through glial fibrillary acidic protein, associated with phosphorylated tau 217 concentration, and in those with mild cognitive impairment, there was a direct effect of WMH on phosphorylated tau 217 and neurofilament light chain concentrations. There were no associations of WMH with biomarker concentrations among those diagnosed with dementia. The findings from this cross-sectional study suggest that among individuals with Down syndrome, cerebrovascular disease promotes neurodegeneration by increasing astrocytosis and tau pathophysiology in the presymptomatic phases of Alzheimer's disease, but future studies will need to confirm these associations with longitudinal data. This work joins an emerging literature that implicates cerebrovascular disease and its interface with neuroinflammation as a core pathological feature of Alzheimer's disease in adults with Down syndrome.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483038","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}
Brain communicationsPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae257
Tommaso Bocci, Chiara Anselmi, Federico La Torre, Emanuela De Lisa, Giacomo Sabbadin, Matteo Guidetti, Natale Maiorana, Alberto Priori, Lucia Manni
{"title":"Lessons on neurodegeneration and aging from the Lagoon of Venice: the marine invertebrate <i>Botryllus schlosseri</i>.","authors":"Tommaso Bocci, Chiara Anselmi, Federico La Torre, Emanuela De Lisa, Giacomo Sabbadin, Matteo Guidetti, Natale Maiorana, Alberto Priori, Lucia Manni","doi":"10.1093/braincomms/fcae257","DOIUrl":"https://doi.org/10.1093/braincomms/fcae257","url":null,"abstract":"<p><p>In this work, the authors proposed a novel and interesting animal model for studying human neurodegenerative diseases, <i>Botryllus schlosseri</i>, a small invertebrate inhabiting temperate seas worldwide, which shares remarkable similarities with mammals in the expression of genes involved in pathological aging.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334341","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}