| Autor: |
Wen Q; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.; MHeNS, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands., Wittens MMJ; Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610 Antwerpen, Belgium.; Neuroprotection and Neuromodulation (NEUR), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium.; Department of Neurology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussel, Belgium., Engelborghs S; Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610 Antwerpen, Belgium.; Neuroprotection and Neuromodulation (NEUR), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium.; Department of Neurology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussel, Belgium., van Herwijnen MHM; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands., Tsamou M; ToxGenSolutions (TGS), 6229EV Maastricht, The Netherlands., Roggen E; ToxGenSolutions (TGS), 6229EV Maastricht, The Netherlands., Smeets B; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.; MHeNS, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands., Krauskopf J; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands., Briedé JJ; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.; MHeNS, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands. |
| Abstrakt: |
Alzheimer's disease (AD) is the most common cause of dementia. New strategies for the early detection of MCI and sporadic AD are crucial for developing effective treatment options. Current techniques used for diagnosis of AD are invasive and/or expensive, so they are not suitable for population screening. Cerebrospinal fluid (CSF) biomarkers such as amyloid β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau181 (P-tau181) levels are core biomarkers for early diagnosis of AD. Several studies have proposed the use of blood-circulating microRNAs (miRNAs) as potential novel early biomarkers for AD. We therefore applied a novel approach to identify blood-circulating miRNAs associated with CSF biomarkers and explored the potential of these miRNAs as biomarkers of AD. In total, 112 subjects consisting of 28 dementia due to AD cases, 63 MCI due to AD cases, and 21 cognitively healthy controls were included. We identified seven Aβ1-42-associated plasma miRNAs, six P-tau181-associated plasma miRNAs, and nine Aβ1-42-associated serum miRNAs. These miRNAs were involved in AD-relevant biological processes, such as PI3K/AKT signaling. Based on this signaling pathway, we constructed an miRNA-gene target network, wherein miR-145-5p has been identified as a hub. Furthermore, we showed that miR-145-5p performs best in the prediction of both AD and MCI. Moreover, miR-145-5p also improved the prediction performance of the mini-mental state examination (MMSE) score. The performance of this miRNA was validated using different datasets including an RT-qPCR dataset from plasma samples of 23 MCI cases and 30 age-matched controls. These findings indicate that blood-circulating miRNAs that are associated with CSF biomarkers levels and specifically plasma miR-145-5p alone or combined with the MMSE score can potentially be used as noninvasive biomarkers for AD or MCI screening in the general population, although studies in other AD cohorts are necessary for further validation. |
