{ "items": [ "\n\n
Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer\u2019s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals.
\n \n\n \n \nThis presentation was given by Hugh Perry of University of Southampton at the Dementias Platform UK 2018 Annual Conference
\n \n\n \n \nThis presentation on the DPUK Data Portal was given by Dr. Sarah Bauermeister at the Dementias Platform UK Annual Conference 2018
\n \n\n \n \nThis was a presentation given by Dr Catherine Calvin about the DPUK Data Portal at the Dementias Platform UK 2018 Annual Conference
\n \n\n \n \nThis is a presentation/workshop given by Chris Orton on the Dementias Platform UK Data Portal at the 2018 Annual Conference
\n \n\n \n \nThis was a presentation given by Dr Chi-Hun Kim at the DPUK Annual Conference 2018
\n \n\n \n \nThis is a presentation given by Chloe Fawns-Ritchie at the Dementias Platform UK 2018 Annual Conference
\n \n\n \n \nThis was a presentation given by Dr John Isaac at the Dementias Platform UK Annual Conference 2018
\n \n\n \n \nThis paper describes a robust method to derive microglia from human pluripotent stem calls. These microglia were used to study the consequences of missence mutations of the TREM2 receptor implicated in frontotemporal dementia-like syndrome and Nasu- Hakola disease (NHD). The work demonstrated there is a complex and subtle effect of missense TREM2 mutations on microglial function that could be consistent with the delayed clinical symptoms seen in FTD-like syndrome and NHD.
\n \n\n \n \nIntroduction: Prospective, population-based studies can be rich resources for dementia research.\r\nFollow-up in many such studies is through linkage to routinely collected, coded health-care data\r\nsets. We evaluated the accuracy of these data sets for dementia case identification.\r\nMethods: We systematically reviewed the literature for studies comparing dementia coding in\r\nroutinely collected data sets to any expert-led reference standard. We recorded study characteristics\r\nand two accuracy measures\u2014positive predictive value (PPV) and sensitivity.\r\nResults: We identified 27 eligible studies with 25 estimating PPV and eight estimating sensitivity.\r\nStudy settings and methods varied widely. For all-cause dementia, PPVs ranged from 33%\u2013100%,\r\nbut 16/27 were .75%. Sensitivities ranged from 21% to 86%. PPVs for Alzheimer\u2019s disease (range\r\n57%\u2013100%) were generally higher than those for vascular dementia (range 19%\u201391%).\r\nDiscussion: Linkage to routine health-care data can achieve a high PPVand reasonable sensitivity in\r\ncertain settings. Given the heterogeneity in accuracy estimates, cohorts should ideally conduct their\r\nown setting-specific validation.
\n \n\n \n \nIn this validation study, the authors used data from ~17,000 UK Biobank participants to identify participants with one or more dementia codes in primary care, hospital admissions or mortality datasets, and compared the coded data to the full-text medical record. Having validated the accuracy of these datasets, they then developed algorithms that can be applied to identify participants with dementia in UK Biobank and other DPUK cohorts. The authors will continue this promising work by investigating sources of potential bias in the data and the generalisability of these findings to older ages and other geographical areas.
\n \n\n \n \nDefective mitochondrial function attributed to optic atrophy 1 (OPA1) mutations causes primarily optic atrophy and, less commonly, neurodegenerative syndromes. The pathomechanism by which OPA1 mutations trigger diffuse loss of neurons in some, but not all, patients is unknown. Here, we used a tractable induced pluripotent stem cell (iPSC)\u2010based model to capture the biology of OPA1 haploinsufficiency in cases presenting with classic eye disease versus syndromic parkinsonism.
\n \n\n \n \nMicroglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons. Co-cultures retain neuronal maturity and functionality for many weeks. Co-culture microglia express key microglia-specific markers and neurodegenerative disease-relevant genes, develop highly dynamic ramifications, and are phagocytic. Upon activation they become more ameboid, releasing multiple microglia-relevant cytokines. Importantly, co-culture microglia downregulate pathogen-response pathways, upregulate homeostatic function pathways, and promote a more anti-inflammatory and pro-remodeling cytokine response than corresponding monocultures, demonstrating that co-cultures are preferable for modeling authentic microglial physiology.
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