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Projects / Programmes source: ARIS

Early detection of Alzehimer's disease with methylation status of candidate genes in liquid biopsies cfDNA

Research activity

Code Science Field Subfield
3.09.00  Medical sciences  Psychiatry   

Code Science Field
B650  Biomedical sciences  Psychiatry, clinical psychology, psychosomatics 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
Alzheimer's disease, mild cognitive impairment, epigenetics, DNA methylation, free circulating DNA, liquid biopsy
Evaluation (rules)
source: COBISS
Researchers (10)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  21395  PhD Petra Hudler  Medical sciences  Researcher  2018 - 2022  156 
2.  29321  PhD Rok Košir  Cardiovascular system  Researcher  2018 - 2022  90 
3.  38237  PhD Katarina Kouter  Biochemistry and molecular biology  Researcher  2018 - 2020  86 
4.  39409  Nejc Nadižar    Technical associate  2018 - 2022  30 
5.  18323  PhD Peter Pregelj  Psychiatry  Researcher  2018 - 2022  364 
6.  28382  PhD Uršula Prosenc Zmrzljak  Public health (occupational safety)  Researcher  2018 - 2022  91 
7.  22459  PhD Tadeja Režen  Neurobiology  Researcher  2018 - 2022  246 
8.  06013  PhD Damjana Rozman  Biochemistry and molecular biology  Researcher  2018 - 2022  896 
9.  27742  PhD Alja Videtič Paska  Medical sciences  Head  2018 - 2022  222 
10.  22072  PhD Tomaž Zupanc  Medical sciences  Researcher  2018 - 2022  191 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,743 
2.  2802  LABENA trgovina, svetovanje in proizvodnja laboratorijske opreme d.o.o. (Slovene)  Ljubljana  5699479  397 
Abstract
Alzheimer’s disease (AD) is a slow, irreversible, but progressive, complex and multifactorial neurodegenerative disorder, which represents the most common cause of dementia in older population, and a major health problem worldwide. Due to the accelerated aging of human population, it is assumed that the number of AD patients will quadruple by the year 2050. The risk of developing AD significantly increases after 65 years of age, and it reaches up to 31% for individuals beyond age 85. The treatment of AD was not significantly changed or improved in the last decade: it includes acetylcholine esterase inhibitors donepezil, galantamine and rivastigmine, and NMDA receptor antagonist memantine. Although a lot of new drugs with novel mechanism of action were effective in animal models, only a few of them showed clinical efficacy in improving cognitive decline. Main risk factors for AD are older age, genetic predisposition, gender, cardiovascular factors and presence of the mild cognitive impairment (MCI). MCI is characterized by the slight cognitive changes and disruptions that occur in mild changes in memory, the ability to think and to remember. MCI might lead to AD, since a great percent of subjects with MCI (50 % - 65 %) later develop some form of dementia, especially AD. At present, clinical diagnosis of (probable) Alzheimer's disease is established thorough a combination of clinical symptoms, cognitive screening tests, detailed neuropsychological testing and imaging techniques. Tests based on molecular-genetic biology analysis are only entering the routine clinical practice, but are as are other clinical tests, relevant only after the disease has already made considerable progress. In our study we will use most contemporary methods (next generation sequencing, droplet digital PCR) to determine methylation status and single nucleotide polymorphisms of AD candidate genes, catechol-o-methyl transferase and brain-derived neurotrophic factor, in blood-based liquid biopsy samples and cell-free DNA (cfDNA) from plasma in clinically well-defined AD patients and subjects with MCI. The introduction of additional epigenetic markers in a set of clinical tests that are currently in use in the diagnosis of AD would enable a more accurate diagnosis in the early stages of the disease, reducing the number of false-positive and false-negative diagnoses. Determining the differences of white blood cells methylation status and methylation cfDNA as a pool of DNA from distant tissues could confirm existence of the so-called ‘mirror effect’ where the peripheral markers reflect the status of unobtainable tissue for molecular studies. The identification of integrative biomarkers would mean a large step forward for diagnostic procedures of Alzheimer's disease and for the prediction of its progression, probably also for the pre-clinical stages of the disorder like MCI, and through a translation to clinical practice. The purpose of the study is to contribute to better understanding of epigenetic changes and their role in the underlying AD pathophysiology, and behavioural and psychological symptoms of dementia and cognitive decay. The early diagnostics would importantly contribute also to prevention and importantly affect life of AD patients and also their families. More rational pharmacotherapy could therefore ease the burden on the health funds.
Significance for science
There is an unmet need to improve understanding of the molecular, genetic end epigenetic, as well as neuronal and synaptic mechanisms of the AD. Early detection of AD has the potential to significantly improve duration and quality of patient’s life, making this research important for society as a whole. The research, which addresses all aspects of dementia, is of the utmost importance for the aging popilations of Slovenia as well as Croatia, but also of EU, and will affect economic costs in the long term. Furthermore, for development of science in particular, these types of projects are very important in terms of acquiring state of the art technology and training young scientists in these techniques to ensure international competitiveness. The innovative design and cutting-edge technology used in this project will put us in the forefront of dementia research. In addition, this project will establish collaboration with international groups thus allowing further training and scientific development of our scientists. Communication and outreach of the results will be provided through scientific publications, lectures, and presentations of the results at national and international conferences. The new knowledge acquired during this project will be used for BSc, MSc or PhD theses, and disseminated through original scientific articles and case reports, in international scientific journals, presentations at scientific meetings and presentations for the patients, caregivers, family and the public. The project findings will have a significant positive impact on public health. Further understanding of dementias is crucial to all western countries since AD affects 1 out of 10 people over 65 years. We expect that the results of this project will reach policy makers at national and international levels as they contribute to an evidence-based foundation of recommendations regarding the early diagnosis of AD, and possible improvement of treatment options. The success of the project will be determined by monitoring the key performance indicators. Finally, there is a potential for the significant knowledge transfer, since the project might lead to some important advancement in science and technology. Namely, biomarkers discovered in course of this project have the potential to be further developed into diagnostic and prognostic kits, after validation studies. Therefore, the potential benefit of the project is also in its clinical application. Additionally, these biomarkers, if validated, might be offered to international/foreign sources to attain additional funding. The project findings might enable the participants to be competitive for further funding, allowing them to expand this approach with a longitudinal follow-up studies in patients with AD.
Significance for the country
There is an unmet need to improve understanding of the molecular, genetic end epigenetic, as well as neuronal and synaptic mechanisms of the AD. Early detection of AD has the potential to significantly improve duration and quality of patient’s life, making this research important for society as a whole. The research, which addresses all aspects of dementia, is of the utmost importance for the aging popilations of Slovenia as well as Croatia, but also of EU, and will affect economic costs in the long term. Furthermore, for development of science in particular, these types of projects are very important in terms of acquiring state of the art technology and training young scientists in these techniques to ensure international competitiveness. The innovative design and cutting-edge technology used in this project will put us in the forefront of dementia research. In addition, this project will establish collaboration with international groups thus allowing further training and scientific development of our scientists. Communication and outreach of the results will be provided through scientific publications, lectures, and presentations of the results at national and international conferences. The new knowledge acquired during this project will be used for BSc, MSc or PhD theses, and disseminated through original scientific articles and case reports, in international scientific journals, presentations at scientific meetings and presentations for the patients, caregivers, family and the public. The project findings will have a significant positive impact on public health. Further understanding of dementias is crucial to all western countries since AD affects 1 out of 10 people over 65 years. We expect that the results of this project will reach policy makers at national and international levels as they contribute to an evidence-based foundation of recommendations regarding the early diagnosis of AD, and possible improvement of treatment options. The success of the project will be determined by monitoring the key performance indicators. Finally, there is a potential for the significant knowledge transfer, since the project might lead to some important advancement in science and technology. Namely, biomarkers discovered in course of this project have the potential to be further developed into diagnostic and prognostic kits, after validation studies. Therefore, the potential benefit of the project is also in its clinical application. Additionally, these biomarkers, if validated, might be offered to international/foreign sources to attain additional funding. The project findings might enable the participants to be competitive for further funding, allowing them to expand this approach with a longitudinal follow-up studies in patients with AD.
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