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- Bergström, Sofia
(författare)
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Multiplexed antibody-based protein profiling in the pursuit of CSF biomarkers for neurodegenerative diseases
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a desire for a transition from generic treatments designed for the average patient, towards more individual-based precision medicine. An increased knowledge about disease pathophysiology on a molecular level would be beneficial for this transition. The study of proteins can contribute with valuable insights into etiology and pathogenesis of different diseases and thereby aid the clinical assessment of patients and guide future treatments.Neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia, are characterized by a progressive loss of function, and eventually death of neurons. Neurons allow the brain to communicate with the rest of the body, and a deteriorated function of neurons can result in problems with mobility or mental functions. Neurodegenerative diseases progress slowly over many years, with a long silent asymptomatic phase before symptom onset. It is hard to rebuild what is already lost, but disease-modifying treatments might be able to slow down or halt the deterioration of the brain. Therefore, there is a major research focus on investigating the early stages of disease pathogenesis in order to elucidate this critical phase in disease progression.The four papers included in this thesis focus on identifying altered protein profiles in cerebrospinal fluid from patients with neurodegenerative diseases. For this purpose, multiplexed antibody-based suspension bead arrays have been used. This method allows for hundreds of proteins to be analyzed in hundreds of samples in the same assay. Paper I focuses on Alzheimer’s disease and investigates the profiles of 200 proteins when comparing patients with controls. Six proteins were identified at altered levels and were further investigated in relation to the progression from mild cognitive impairment to Alzheimer’s disease. Paper II explores 100 protein profiles in relation to the core Alzheimer’s disease biomarkers in asymptomatic 70-year-olds to elucidate patterns preceding potential disease onset. Paper III investigates the transition to cognitive impairment in patients with Parkinson’s disease and explores potential associations between protein profiles and cognitive assessment tests. Finally, Paper IV explores panels of proteins in the context of frontotemporal dementia. Panels of proteins, instead of single biomarkers, have an increased potential to capture the range of biological processes within these types of complex and multifactorial diseases.Neurodegenerative diseases are often heterogeneous which puts high demands on the study design including an appropriate selection of study population. However, significant similarities are also present which makes it advantageous to have a broad perspective and work with several neurodegenerative disorders. This thesis presents the results from multiplexed antibody-based protein profiling as a contribution to a better understanding of neurodegenerative diseases.
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| 2. |
- Schell, Carl Otto, et al.
(författare)
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The global need for essential emergency and critical care
- 2018
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Critical illness results in millions of deaths each year. Care for those with critical illness is often neglected due to a lack of prioritisation, co-ordination, and coverage of timely identification and basic life-saving treatments. To improve care, we propose a new focus on essential emergency and critical care (EECC)care that all critically ill patients should receive in all hospitals in the world. Essential emergency and critical care should be part of universal health coverage, is appropriate for all countries in the world, and is intended for patients irrespective of age, gender, underlying diagnosis, medical specialty, or location in the hospital. Essential emergency and critical care is pragmatic and low-cost and has the potential to improve care and substantially reduce preventable mortality.
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