Project description:With the aging population, there is a growing focus on dementia, especially Alzheimer’s disease (AD). The molecular basis underlying the pathogenesis of AD is gradually being elucidated. Increasing evidence has shown that the immunological function of leukocytes plays a crucial role in the development of neurodegenerative disorders. However, there have been few studies among the Taiwanese population. The aim of this study was to investigate potential biomarkers for early diagnosis of Alzheimer’s disease from blood leukocytes. Experiment Overall Design: The peripheral blood mononuclear cells (PBMC) transcriptomes from 5 patients with mild cognitive impairment (MCI), 4 AD, as well as 4 normal controls (NC), were analyzed by microarray analysis.
Project description:Mild cognitive impairment (MCI) is considered an early stage leading to dementia. MCI can be reversed, and early diagnosis at the MCI stage is vital to control the progression to dementia. Dementia is currently diagnosed based on interviews and screening tests. However, novel biomarkers must be identified to enable early detection of MCI. Therefore, this study aimed to discover novel biomarkers in the form of blood microRNAs (miRNAs) for the diagnosis of MCI or early dementia.
Project description:Using WGCNA and enrichment analyses to identify pathway level differences between individuals with no cognitive impairment, mild cognitive impairment, and Alzheimer’s disease. Frozen frontal cortex (BA10) tissue from NCI, MCI, and mild/moderate AD cases (n = 12/group) representing both genders was acquired postmortem from participants in the Rush Religious Orders Study, a longitudinal clinical pathologic study of aging and AD in elderly Catholic clergy
Project description:Growing evidence implicates transposable elements (TEs) in aging and Alzheimer’s disease (AD). To evaluate potential transcriptional and epigenetic differences related to TE expression in this context, we generated whole blood total RNA-seq, and peripheral blood cell whole-genome bisulfite sequencing (WGBS), and transposase-accessible chromatin sequencing (ATAC-seq) on samples from healthy middle-aged/older adults, mild cognitive impairment (MCI), and AD patients.
Project description:Genome-wide profiling of DNA methylation in blood leukocytes from Chinese patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The Illumina Infinium MethylationEPIC BeadChip array (850K chip) was used to detect DNA methylation profiles throughout approximately 850,000 CpG sites in peripheral blood white cells of MCI- and AD-affected Chinese patients, as well as cognitively healthy controls. All samples included 20 Chinese patients with MCI, 20 Chinese patients with AD, and 20 cognitively healthy controls.
Project description:MicroRNAs (miRNAs) could play an important role as potential Alzheimer Disease (AD) biomarkers. Plasma samples were collected from participants: Mild cognitive impairment (MCI) due to AD patients (n= 20), preclinical AD patients (n= 8) and healthy controls (n= 20). Then, small RNA sequencing analysis, followed by miRNA differential expression analysis comparing different methods (DESeq2, edgeR, NOISeq) were carried out.
Project description:Human serum samples from Alzheimer's disease driven mild cognitive impairment and non-diseased controls were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. Other neurodegenerative and non-neurodegenerative diseases were also used to help measure the specificity of the selected biomarkers.
Project description:Background: Mild cognitive impairment (MCI) is an intermediate state between normal aging, and Alzheimer’s disease, and other dementias. Early detection of dementia, and MCI, is a crucial issue in terms of secondary prevention. Blood biomarker detection is a possible way for early detection of MCI. Although disease biomarkers are detected by, in general, using single molecular analysis such as t-test, another possible approach is based on interaction between molecules. Results: Differential correlation analysis, which detects difference on correlation of two variables in case/control study, was carried out to the dataset with 745 microRNAs (miRNAs) from plasma samples of 30 age-matched controls and 23 MCI patients in Japan. The 20 pairs of miRNAs, which consist of 20 miRNAs, were selected as MCI markers. Two pairs of miRNAs (hsa-miR-191 and hsa-miR-101, and hsa-miR-103 and hsa-miR-222) out of 20 attained the highest area under the curve (AUC) value of 0.962 for MCI detection. Other two miRNA pairs that include hsa-miR-191 and hsa-miR-125b also attained high AUC value of ≥ 0.95. Pathway analysis was performed to the MCI markers for further understanding of biological implications. As a result, collapsed correlation on hsa-miR-191 and emerged correlation on hsa-miR-125b may have key role in MCI, and dementia progression. Conclusion: Differential correlation analysis, a bioinformatics tool to elucidate complicated and interdependent biological systems behind diseases, detects effective MCI markers that cannot be found by single molecule analysis such as t-test.
Project description:Alzheimer case-control samples originate from the EU funded AddNeuroMed Cohort, which is a large cross-European AD biomarker study relying on human blood as the source of RNA. The design is case-control. Cases are either Alzheimer's disease patients, subjects with mild cognitive impairment or age and gender matched controls.
