| 1. |
- Chen, Z. C., et al.
(författare)
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Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:3, s. 487-496
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest in measuring tau in blood and cerebrospinal fluid (CSF). Methods: We developed a set of immunoassays to measure tau in specimens from humans diagnosed based on current best clinical and CSF biomarker criteria. Results: In CSF, mid-region- and N-terminal-detected tau predominated and rose in disease. In plasma, an N-terminal assay (NT1) detected elevated levels of tau in AD and AD-mild cognitive impairment (MCI). Plasma NT1 measurements separated controls from AD-MCI (area under the curve [AUC] = 0.88) and AD (AUC = 0.96) in a discovery cohort and in a Validation Cohort (with AUCs = 0.79 and 0.75, respectively). Discussion: The forms of tau in CSF and plasma are distinct, but in each specimen type, the levels of certain fragments are increased in AD. Measurement of plasma NT1 tau should be aggressively pursued as a potential blood-based screening test for AD/AD-MCI. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
- Brinkmalm, Gunnar, et al.
(författare)
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Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer's brain
- 2019
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 142:5, s. 1441-1457
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Tidskriftsartikel (refereegranskat)abstract
- The primary structure of canonical amyloid-β-protein was elucidated more than 30 years ago, yet the forms of amyloid-β that play a role in Alzheimer's disease pathogenesis remain poorly defined. Studies of Alzheimer's disease brain extracts suggest that amyloid-β, which migrates on sodium dodecyl sulphate polyacrylamide gel electrophoresis with a molecular weight of ∼7 kDa (7kDa-Aβ), is particularly toxic; however, the nature of this species has been controversial. Using sophisticated mass spectrometry and sensitive assays of disease-relevant toxicity we show that brain-derived bioactive 7kDa-Aβ contains a heterogeneous mixture of covalently cross-linked dimers in the absence of any other detectable proteins. The identification of amyloid-β dimers may open a new phase of Alzheimer's research and allow a better understanding of Alzheimer's disease, and how to monitor and treat this devastating disorder. Future studies investigating the bioactivity of individual dimers cross-linked at known sites will be critical to this effort. © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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| 3. |
- Lauwers, E., et al.
(författare)
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Potential human transmission of amyloid beta pathology: surveillance and risks
- 2020
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:10, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid beta after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid beta through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid beta might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid beta transmission and to clarify whether other similar proteopathic seeds, such as tau or alpha-synuclein, can also be transferred iatrogenically.
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| 4. |
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| 5. |
- Donovan, Mary K., et al.
(författare)
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Combining fish and benthic communities into multiple regimes reveals complex reef dynamics
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Coral reefs worldwide face an uncertain future with many reefs reported to transition from being dominated by corals to macroalgae. However, given the complexity and diversity of the ecosystem, research on how regimes vary spatially and temporally is needed. Reef regimes are most often characterised by their benthic components; however, complex dynamics are associated with losses and gains in both fish and benthic assemblages. To capture this complexity, we synthesised 3,345 surveys from Hawai'i to define reef regimes in terms of both fish and benthic assemblages. Model-based clustering revealed five distinct regimes that varied ecologically, and were spatially heterogeneous by island, depth and exposure. We identified a regime characteristic of a degraded state with low coral cover and fish biomass, one that had low coral but high fish biomass, as well as three other regimes that varied significantly in their ecology but were previously considered a single coral dominated regime. Analyses of time series data reflected complex system dynamics, with multiple transitions among regimes that were a function of both local and global stressors. Coupling fish and benthic communities into reef regimes to capture complex dynamics holds promise for monitoring reef change and guiding ecosystem-based management of coral reefs.
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| 6. |
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| 7. |
- Jouffray, Jean-Baptiste, et al.
(författare)
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Parsing human and biophysical drivers of coral reef regimes
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1896
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Tidskriftsartikel (refereegranskat)abstract
- Coral reefs worldwide face unprecedented cumulative anthropogenic effects of interacting local human pressures, global climate change and distal social processes. Reefs are also bound by the natural biophysical environment within which they exist. In this context, a key challenge for effective management is understanding how anthropogenic and biophysical conditions interact to drive distinct coral reef configurations. Here, we use machine learning to conduct explanatory predictions on reef ecosystems defined by both fish and benthic communities. Drawing on the most spatially extensive dataset available across the Hawaiian archipelago-20 anthropogenic and biophysical predictors over 620 survey sites-we model the occurrence of four distinct reef regimes and provide a novel approach to quantify the relative influence of human and environmental variables in shaping reef ecosystems. Our findings highlight the nuances of what underpins different coral reef regimes, the overwhelming importance of biophysical predictors and how a reef's natural setting may either expand or narrow the opportunity space for management interventions. The methods developed through this study can help inform reef practitioners and hold promises for replication across a broad range of ecosystems.
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