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Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP
Granic A, Padmanabhan J, Norden M, Potter H.. Molecular biology of the cell, 2009-12-23
Topic: Brain proteins, microglia and lab models
Both sporadic and familial Alzheimer's disease (AD) patients exhibit increased chromosome aneuploidy, particularly trisomy 21, in neurons and other cells. Significantly, trisomy 21/Down syndrome patients develop early onset AD pathology. We investigated the mechanism underlying mosaic chromosome aneuploidy in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice and in transfected cells. Furthermore, adding synthetic Abeta peptide, the pathogenic product of APP, to cultured cells causes rapid and robust chromosome mis-segregation leading to aneuploid, including trisomy 21, daughters, which is prevented by LiCl addition or Ca(2+) chelation and is replicated in tau KO cells, implicating GSK-3beta, calpain, and Tau-dependent microtubule transport in the aneugenic activity of Abeta. Furthermore, APP KO cells are resistant to the aneugenic activity of Abeta, as they have been shown previously to be resistant to Abeta-induced tau phosphorylation and cell toxicity. These results indicate that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may thereby contribute to the pathogenesis of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Granic, A., Padmanabhan, J., Norden, M., & Potter, H. (2010). Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP. Molecular biology of the cell. https://doi.org/10.1091/mbc.e09-10-0850
Vancouver
Granic A, Padmanabhan J, Norden M, Potter H. Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP. Molecular biology of the cell. 2010. doi:10.1091/mbc.e09-10-0850. PMID: 20032300.
BibTeX
@article{granic2010-20032300,
author = {Granic, A. and Padmanabhan, J. and Norden, M. and Potter, H.},
title = {{Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP}},
journal = {Molecular biology of the cell},
year = {2010},
doi = {10.1091/mbc.e09-10-0850},
pmid = {20032300},
url = {https://doi.org/10.1091/mbc.e09-10-0850}
}
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Key findings
- Significantly, trisomy 21/Down syndrome patients develop early onset AD pathology.
- These results indicate that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may thereby contribute to the pathogenesis of AD.
Why it matters
In transgenic mice and transfected cells, familial Alzheimer's disease mutations in APP induced chromosome mis-segregation and aneuploidy, and adding synthetic amyloid-beta peptide to cultured cells caused rapid chromosome mis-segregation including trisomy 21. The authors conclude that amyloid-beta-induced microtubule dysfunction leads to aneuploid neurons and may contribute to the pathogenesis of Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular biology of the cell) |
| Journal's citation record | 3 / 4 | Molecular Biology of the Cell: journal h-index 297 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 81 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 3.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Huntington Potter: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of South Florida: institution h-index 806 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20032300) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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