A human stem cell model of early Alzheimer's disease pathology in Down syndrome.

Science Translational Medicine
Yichen ShiFrederick J Livesey

Abstract

Human cellular models of Alzheimer's disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset AD, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP). We found that cortical neurons generated from iPS cells and embryonic stem cells from Down syndrome patients developed AD pathologies over months in culture, rather than years in vivo. These cortical neurons processed the transmembrane APP protein, resulting in secretion of the pathogenic peptide fragment amyloid-β42 (Aβ42), which formed insoluble intracellular and extracellular amyloid aggregates. Production of Aβ peptides was blocked by a γ-secretase inhibitor. Finally, hyperphosphorylated tau protein, a pathological hallmark of AD, was found to be localized to cell bodies and dendrites in iPS cell-derived cortical neurons from Down syndrome patients, recapitulating later st...Continue Reading

References

Jun 1, 1989·The New England Journal of Medicine·B RumbleC L Masters
Aug 2, 1996·The Journal of Biological Chemistry·D J Selkoe
Jul 18, 2000·Journal of Intellectual Disability Research : JIDR·A J HollandF Stevens
Dec 15, 2000·Journal of Intellectual Disability Research : JIDR·S Gravestock
Dec 12, 2001·The Biochemical Journal·J HilpertT E Willnow
Feb 9, 2007·Journal of Neurochemistry·Dominic M Walsh, Dennis J Selkoe
Aug 9, 2007·Nature Reviews. Neuroscience·Carlo BallatoreJohn Q Trojanowski
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lina ChakrabartiTarik F Haydar
Aug 12, 2008·Cell·In-Hyun ParkGeorge Q Daley
Sep 20, 2008·Nature Reviews. Neuroscience·Lars Bertram, Rudolph E Tanzi
Mar 20, 2009·Human Molecular Genetics·Frances K WisemanElizabeth M C Fisher
May 22, 2009·Journal of Neurochemistry·John Hardy
Dec 3, 2009·Cell Stem Cell·Krishanu Saha, Rudolf Jaenisch
Jan 26, 2010·Progress in Neurobiology·Andrea ContestabileLaura Gasparini
Mar 27, 2010·Nature Reviews. Drug Discovery·Allison D Ebert, Clive N Svendsen
Jun 16, 2010·Neuron·Karen H Ashe, Kathleen R Zahs
Jul 20, 2010·Nature Neuroscience·Lina ChakrabartiTarik F Haydar
Mar 9, 2011·Neuron·Tarran PierfeliceNicholas Gaiano
May 18, 2011·Cold Spring Harbor Perspectives in Biology·Dennis J Selkoe
Jun 3, 2011·The New England Journal of Medicine·Christine Mummery
Jun 10, 2011·Nature Biotechnology·Kristen Martins-TaylorRen-He Xu
Sep 9, 2011·Human Molecular Genetics·Takuya YagiNorihiro Suzuki
Jan 27, 2012·Nature·Mason A IsraelLawrence S B Goldstein
Feb 10, 2012·Nature

❮ Previous
Next ❯

Citations

Jun 15, 2012·Journal of Neural Transmission·Lezanne OoiGerald Münch
May 9, 2013·Ageing Research Reviews·Shauna H Yuan, Mason Shaner
Jul 19, 2013·Nature·Jun JiangJeanne B Lawrence
Oct 10, 2013·Nature Biotechnology·Ruth McKernan, Fiona M Watt
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Glenn A MacleanStuart H Orkin
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jason P WeickAnita Bhattacharyya
Aug 7, 2012·Human Molecular Genetics·Jessica E Young, Lawrence S B Goldstein
May 19, 2012·Alzheimer's Research & Therapy·Douglas GalaskoGordon Wilcock
Nov 8, 2012·Alzheimer's Research & Therapy·Frederick J Livesey
Nov 29, 2012·Alzheimer's Research & Therapy·Sharon J Sha, Adam Boxer
Mar 29, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Herman van der Putten, Gregor P Lotz
Aug 7, 2014·Trends in Pharmacological Sciences·Ralf HeilkerJared Sterneckert
Aug 14, 2012·Neural Plasticity·Hansen Wang, Laurie C Doering
Jul 30, 2014·Nature Reviews. Genetics·Jared L SterneckertHans R Schöler
Aug 6, 2014·Nature Biotechnology·Ken Garber
Aug 15, 2015·International Journal of Molecular Sciences·Atsushi TanakaKeiichi Fukuda
Aug 5, 2015·Journal of Clinical Medicine·Youssef Hibaoui, Anis Feki
Dec 7, 2013·Expert Opinion on Drug Discovery·Henrik Landgren, Peter Sartipy
Feb 18, 2016·Stem Cells International·Nina Xie, Beisha Tang
Nov 4, 2015·Frontiers in Behavioral Neuroscience·Xun Yu ChoongElizabeth M C Fisher
Aug 6, 2015·Nature Reviews. Neuroscience·Frances K WisemanAndré Strydom
Aug 5, 2015·Stem Cells International·Wenbin WanXiantao Tai
Apr 9, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Allan Acab, Alysson Renato Muotri
Jun 13, 2015·Nature Protocols·Young Hye KimDoo Yeon Kim
Jun 6, 2015·Alzheimer's Research & Therapy·Vorapin ChinchalongpornOttavio Arancio
Aug 12, 2014·Genomics, Proteomics & Bioinformatics·Guangchun HanHongxing Lei
May 6, 2014·Frontiers in Cellular Neuroscience·Miguel Medina, Jesús Avila
Jan 1, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Tae-Wan Kim
Dec 24, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Lawrence S B GoldsteinGrace Woodruff
Aug 29, 2014·PloS One·Christina R MuratoreTracy L Young-Pearse
Dec 29, 2016·Nature Reviews. Genetics·Stylianos E Antonarakis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.