| 1. |
- Paterson, R. W., et al.
(author)
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SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases
- 2019
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In: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 15:7, s. 419-427
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Journal article (peer-reviewed)abstract
- Alzheimer disease (AD) is one of several neurodegenerative diseases characterized by dysregulation, misfolding and accumulation of specific proteins in the CNS. The stable isotope labelling kinetics (SILK) technique is based on generating amino acids labelled with naturally occurring stable (that is, nonradioactive) isotopes of carbon and/or nitrogen. These labelled amino acids can then be incorporated into proteins, enabling rates of protein production and clearance to be determined in vivo and in vitro without the use of radioactive or chemical labels. Over the past decade, SILK studies have been used to determine the turnover of key pathogenic proteins amyloid-β (Aβ), tau and superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of healthy individuals, patients with AD and those with other neurodegenerative diseases. These studies led to the identification of several factors that alter the production and/or clearance of these proteins, including age, sleep and disease-causing genetic mutations. SILK studies have also been used to measure Aβ turnover in blood and within brain tissue. SILK studies offer the potential to elucidate the mechanisms underlying various neurodegenerative disease mechanisms, including neuroinflammation and synaptic dysfunction, and to demonstrate target engagement of novel disease-modifying therapies. © 2019, Springer Nature Limited.
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| 2. |
- Alcolea, D., et al.
(author)
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Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias
- 2021
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:11, s. 1206-1214
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Journal article (peer-reviewed)abstract
- Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach. Methods: We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination. Results: The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001). Conclusions: Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 3. |
- Delaby, C., et al.
(author)
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Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles
- 2022
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In: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 129, s. 231-237
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Journal article (peer-reviewed)abstract
- Introduction Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined. Methods We studied in two independent cohorts, the performance of blood biomarkers in detecting "nonpathological" (A-/T-/N-), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles. Results Plasma A beta(1-42)/A beta(1-40) ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A-/T-/N-) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection. Conclusion The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents an attractive stratification strategy in the clinical management of patients visiting memory clinics. This could reduce the need for lumbar puncture and foreshadow the use of blood testing on larger populations.
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| 4. |
- Bennett, Deborah, et al.
(author)
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Project TENDR : Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement
- 2016
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In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Science. - 0091-6765 .- 1552-9924. ; 124:7, s. A118-A122
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Journal article (peer-reviewed)abstract
- Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes-genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children's health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children's brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children's risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
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| 5. |
- Melin, Jeanette, et al.
(author)
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Metrological references for person ability in memory tests
- 2021
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In: Measurement: Sensors. - : Elsevier Ltd. - 2665-9174. ; 18
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Journal article (peer-reviewed)abstract
- To ensure reliable diagnosis and treatment consistently throughout healthcare, metrological quality assurance is essential. There are, however, many observations in the social sciences and healthcare, such as the memory tests studied here, which have been ‘claimed’ to be measurements but in fact have not been fully metrologically legitimated. We have already argued in favour of extending traditional metrological underlying principles to cover social measurements, including the development of construct specification equations (CSE) considered as ‘recipes for certified reference materials (CRM)’ for traceability, analogous to CRMs in metrology in chemistry. Although the CSE approach has to date been used mostly to explain and validate test item attributes, this paper turns to focus on causal explanations of person characteristics. We describe methods and preliminary results developed in the European EMPIR NeuroMET projects, which may be used for providing quality assured measurement of disease progression and treatment benefits for patients with neurodegenerative conditions.
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| 6. |
- Vicente Perez-Giron, J., et al.
(author)
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Selective binding of oligonucleotide on TiO2 surfaces modified by swift heavy ion beam lithography
- 2014
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In: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier. - 0168-583X .- 1872-9584. ; 339, s. 67-74
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Journal article (peer-reviewed)abstract
- We have used swift heavy-ion beam based lithography to create patterned bio-functional surfaces on rutile TiO2 single crystals. The applied lithography method generates a permanent and well defined periodic structure of micrometre sized square holes having nanostructured TiO2 surfaces, presenting different physical and chemical properties compared to the surrounding rutile single crystal surface. On the patterned substrates selective binding of oligonucleotides molecules is possible at the surfaces of the holes. This immobilisation process is only being controlled by UV light exposure. The patterned transparent substrates are compatible with fluorescence detection techniques, are mechanically robust, have a high tolerance to extreme chemical and temperature environments, and apparently do not degrade after ten cycles of use. These qualities make the patterned TiO2 substrates useful for potential biosensor applications.
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