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Molecular and neuroimaging biomarkers in the differentiation of patients who convert to Alzheimer's disease

Grant number: 19/13003-4
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): October 01, 2019
Effective date (End): March 16, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Marcio Luiz Figueredo Balthazar
Grantee:Thamires Naela Cardoso Magalhães
Supervisor abroad: Charlotte Teunissen
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of Amsterdam (UvA), Netherlands  
Associated to the scholarship:17/13906-9 - Predictors of functional and structural neuroimaging in conversion of mild cognitive impairment to dementia of Alzheimer's Disease according to AT(N) classification, BP.DR

Abstract

Alzheimer's disease (AD) dementia is a neurodegenerative disease characterized by progressive brain atrophy and cognitive decline. Although AD is defined by the excessive amount of neuritic plaques and neurofibrillary tangles, the complete neurodegenerative process is much more complex and not fully understood. The most accepted models of AD progression indicate that pathophysiological changes start decades before clinical symptoms. In clinical terms, AD dementia is preceded by a possible prodromal phase, namely mild cognitive impairment (MCI). The development of more sensitive biomarkers of AD is essential to perform an early diagnosis and, with the potential emergence of new drugs, they may be essential to prevent the neurodegenerative process. In this sense, the focus of AD diagnostic research is to deepen the study of molecular biomarkers in the earliest phases of cognitive decline. A technical challenge in the field is to discover reliable non-invasive plasmatic biomarkers with high predictive value of conversion to AD. However, a major challenge in developing blood biomarkers is that brain-specific proteins reflect AD molecular mechanisms at much lower concentrations in blood than in cerebrospinal fluid (CSF). Although plasmatic AD markers, until this moment, have failed to be trustworthy biomarkers, new technologies may help to resolve this problem. Quanterix-Simoa (single molecule array) HD-1 Analyzer is a fully automated method, with higher sensitivity and precision. This technology may improve the plasmatic detection of molecular biomarkers. Furthermore, molecular changes have also been associated with neuroimaging biomarkers. Together they could improve the accuracy of prediction of conversion from MCI to dementia. The main question of our research project is: what are the best biomarkers (molecular and neuroimaging) for the prediction of cognitive decline and conversion to dementia among MCI patients? To answer this question, we selected both well-established and new promising biomarkers in different AD pathophysiological processes: a) structural and functional magnetic resonance imaging; b) CSF and plasmatic high-sensitive analyses of AD markers (amyloid-beta (A²42) and t-Tau proteins); c) CSF analyses of synaptic dysfunction markers (visinin-like protein 1 (VILIP-1) and neurogranin); and d) plasmatic analyses of possible inflammatory markers (neurofilament light chain (NFL), triggering receptor expressed on myeloid cells 2 (TREM2) and complement c3).

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