| 1. |
- Lashley, T., et al.
(författare)
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Molecular biomarkers of Alzheimer's disease: progress and prospects
- 2018
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Ingår i: Disease Models & Mechanisms. - : The Company of Biologists. - 1754-8403 .- 1754-8411. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- The neurodegenerative disorder Alzheimer's disease is characterised by the formation of beta-amyloid plaques and neurofibrillary tangles in the brain parenchyma, which cause synapse and neuronal loss. This leads to clinical symptoms, such as progressive memory deficits. Clinically, these pathological changes can be detected in the cerebrospinal fluid and with brain imaging, although reliable blood tests for plaque and tangle pathologies remain to be developed. Plaques and tangles often co-exist with other brain pathologies, including aggregates of transactive response DNA-binding protein 43 and Lewy bodies, but the extent to which these contribute to the severity of Alzheimer's disease is currently unknown. In this 'At a glance' article and poster, we summarise the molecular biornarkers that are being developed to detect Alzheimer's disease and its related pathologies. We also highlight the biornarkers that are currently in clinical use and include a critical appraisal of the challenges associated with applying these biornarkers for diagnostic and prognostic purposes of Alzheimer's disease and related neurodegenerative disorders, also in their prodromal clinical phases.
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| 2. |
- Paterson, Ross W, et al.
(författare)
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Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic
- 2018
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias.We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n=156), DLB (n=20), behavioural variant frontotemporal dementia (bvFTD; n=45), progressive non-fluent aphasia (PNFA; n=17), and semantic dementia (SD; n=7); approximately 10% were pathology/genetically confirmed (n=26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n=104), DLB (n=5), bvFTD (n=12), PNFA (n=3), SD (n=9), and controls (n=10).There were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity >50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort.CSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA.
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| 3. |
- Toombs, J., et al.
(författare)
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Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios
- 2018
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 10, s. 311-321
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. Methods: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ42, Aβ40, and Aβ38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay. Data were analyzed using mixed models in R. Results: Decrease of measurable Aβ peptide concentrations was exaggerated in longer peptides, affecting the Aβ42:Aβ40 and Aβ42:Aβ38 ratios. However, the effect size of surface treatment was reduced in Aβ peptide ratios versus Aβ42 alone. For Aβ42:Aβ40, the effect was reduced by approximately 50% (volume) and 75% (transfer) as compared to Aβ42 alone. Discussion: Use of Aβ ratios, in conjunction with concentrations, may mitigate confounding factors and assist the clinical diagnostic process for Alzheimer's disease.
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| 4. |
- Strohmayer, A., et al.
(författare)
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CHIversity : Implications for equality, diversity, and inclusion campaigns
- 2018
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Ingår i: Proceeding CHI EA '18 Extended Abstracts of the 2018 CHI Conference on Human Factors in Computing Systems. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450356206 - 9781450356213
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Konferensbidrag (refereegranskat)abstract
- In this alt.chi paper, we reflect on #CHIversity; a grassroots campaign highlighting feminist issues related to diversity and inclusion at CHI2017, and in HCI more widely. #CHIversity was operationalised through a number of activities including: collaborative cross-stitch and ‘zine’ making events; the development of a ‘Feminist CHI Programme’; and the use of a Twitter hashtag ‘#CHIversity’. These events granted insight into how diversity discourses are approached within the CHI community. From these recognitions we provide examples of how diversity and inclusion can be promoted at future SIGCHI events. These include fostering connections between attendees, discussing ‘polarizing’ research in a conservative political climate, and encouraging contributions to the growing body of HCI literature addressing feminisms and related subjects. Finally, we suggest how these approaches and benefits can translate to HCI events extending beyond CHI, where exclusion may routinely go undetected.
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| 5. |
- Toombs, A. L., et al.
(författare)
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Supporting the complex social lives of new parents
- 2018
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Ingår i: CHI '18 Proceedings of the 2018 CHI Conference on Human Factors in Computing Systems. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450356206 - 9781450356213
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Konferensbidrag (refereegranskat)abstract
- One of the many challenges of becoming a parent is the shift in one's social life. As HCI researchers have begun to investigate the intersection of sociotechnical system design and parenthood, they have also sought to understand how parents' social lives can be best supported. We build on these strands of research through a qualitative study with new parents regarding the role of digital technologies in their social lives as they transition to parenthood. We demonstrate how sociotechnical systems are entangled in the ways new parents manage their relationships, build (or resist building) new friendships and ad hoc support systems, and navigate the vulnerabilities of parenthood. We discuss how systems designed for new parents can better support the vulnerabilities they internalize, the diverse friendships they desire, and the logistical challenges they experience. We conclude with recommendations for future design and research in this area.
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