Title |
Integrated biology approach reveals molecular and pathological interactions among Alzheimer’s Aβ42, Tau, TREM2, and TYROBP in Drosophila models
|
---|---|
Published in |
Genome Medicine, March 2018
|
DOI | 10.1186/s13073-018-0530-9 |
Pubmed ID | |
Authors |
Michiko Sekiya, Minghui Wang, Naoki Fujisaki, Yasufumi Sakakibara, Xiuming Quan, Michelle E. Ehrlich, Philip L. De Jager, David A. Bennett, Eric E. Schadt, Sam Gandy, Kanae Ando, Bin Zhang, Koichi M. Iijima |
Abstract |
Cerebral amyloidosis, neuroinflammation, and tauopathy are key features of Alzheimer's disease (AD), but interactions among these features remain poorly understood. Our previous multiscale molecular network models of AD revealed TYROBP as a key driver of an immune- and microglia-specific network that was robustly associated with AD pathophysiology. Recent genetic studies of AD further identified pathogenic mutations in both TREM2 and TYROBP. In this study, we systematically examined molecular and pathological interactions among Aβ, tau, TREM2, and TYROBP by integrating signatures from transgenic Drosophila models of AD and transcriptome-wide gene co-expression networks from two human AD cohorts. Glial expression of TREM2/TYROBP exacerbated tau-mediated neurodegeneration and synergistically affected pathways underlying late-onset AD pathology, while neuronal Aβ42 and glial TREM2/TYROBP synergistically altered expression of the genes in synaptic function and immune modules in AD. The comprehensive pathological and molecular data generated through this study strongly validate the causal role of TREM2/TYROBP in driving molecular networks in AD and AD-related phenotypes in flies. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 30% |
United States | 3 | 30% |
Canada | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 50% |
Scientists | 5 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 94 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 19 | 20% |
Student > Ph. D. Student | 15 | 16% |
Student > Master | 11 | 12% |
Professor | 6 | 6% |
Student > Bachelor | 4 | 4% |
Other | 13 | 14% |
Unknown | 26 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 27 | 29% |
Biochemistry, Genetics and Molecular Biology | 14 | 15% |
Agricultural and Biological Sciences | 7 | 7% |
Medicine and Dentistry | 5 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Other | 9 | 10% |
Unknown | 29 | 31% |