| Title |
Modeling Alzheimer’s Disease by Induced Pluripotent Stem Cells Carrying APP D678H Mutation
|
|---|---|
| Published in |
Molecular Neurobiology, September 2018
|
| DOI | 10.1007/s12035-018-1336-x |
| Pubmed ID | |
| Authors |
Kuo-Hsuan Chang, Guey-Jen Lee-Chen, Ching-Chang Huang, Jia-Li Lin, Yi-Jing Chen, Pei-Chi Wei, Yen-Shi Lo, Chin-Fa Yao, Ming-Wei Kuo, Chiung-Mei Chen |
| Abstract |
Alzheimer's disease (AD), probably caused by abnormal accumulation of β-amyloid (Aβ) and aberrant phosphorylation of tau, is the most common cause of dementia among older people. Generation of patient-specific neurons by induced pluripotent stem cell (iPSC) technology facilitates exploration of the disease features in live human neurons from AD patients. In this study, we generated iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant accumulation of intracellular and secreted Aβ42 and Aβ40, reduction of serine 9 phosphorylation in glycogen synthase kinase 3β (GSK3β) hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired neurite outgrowth, downregulation of synaptophysin, and increased caspase 1 activity. The comparison between neurons derived from a sibling pair of wild-type and mutated iPSCs successfully recapitulated these AD phenotypes. Treatment with indole compound NC009-1 (3-((1H-Indole-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one), a potential Aβ aggregation reducer, normalized the Aβ levels and GSK3β and tau phosphorylation, attenuated caspase 1 activity, and improved neurite outgrowth in AD-iPSC-derived neurons. Thus, APP D678H iPSCs-derived neurons recapitulate the cellular characteristics relevant to AD and enable exploration of the underlying pathogenesis and therapeutic strategies for AD. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 17% |
| Australia | 1 | 17% |
| Unknown | 4 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 50% |
| Scientists | 2 | 33% |
| Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 82 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 17 | 21% |
| Student > Ph. D. Student | 15 | 18% |
| Student > Master | 10 | 12% |
| Student > Bachelor | 7 | 9% |
| Student > Doctoral Student | 3 | 4% |
| Other | 10 | 12% |
| Unknown | 20 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 25 | 30% |
| Biochemistry, Genetics and Molecular Biology | 16 | 20% |
| Agricultural and Biological Sciences | 10 | 12% |
| Engineering | 4 | 5% |
| Medicine and Dentistry | 3 | 4% |
| Other | 3 | 4% |
| Unknown | 21 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2019.
All research outputs
#1,778,074
of 23,103,903 outputs
Outputs from Molecular Neurobiology
#147
of 3,499 outputs
Outputs of similar age
#39,764
of 342,063 outputs
Outputs of similar age from Molecular Neurobiology
#7
of 103 outputs
Altmetric has tracked 23,103,903 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,499 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 95% of its peers.
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We're also able to compare this research output to 103 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.