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Journal of Neural Transmission

, Volume 120, Issue 1, pp 103–111 | Cite as

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

  • Lezanne Ooi
  • Kuldip Sidhu
  • Anne Poljak
  • Greg Sutherland
  • Michael D. O’Connor
  • Perminder Sachdev
  • Gerald MünchEmail author
Dementias - Review article

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that leads to a progressive decline in a person’s memory and ability to communicate and carry out daily activities. The brain pathology in AD is characterized by extensive neuronal loss, particularly of cholinergic neurons, intracellular neurofibrillary tangles composed of the tau protein (NFTs) and extracellular deposition of plaques composed of β-amyloid (Aβ), a cleavage product of the amyloid precursor protein (APP). These two insoluble protein aggregates are accompanied by a chronic inflammatory response and extensive oxidative damage. Whereas dys-regulation of APP expression or processing appears to be important for the familial, early-onset form of AD, controversy exists between the “Baptists” (in favour of Aβ) and the “Tauists” (in favour of tau) as to which of these two protein dysfunctions occur at the earliest stages or are the most important contributors to the disease process in sporadic AD. However, more and more “non-amyloid” and “non-tau” causes have been proposed, including, glycation, inflammation, oxidative stress and dys-regulation of the cell cycle. However, to get an insight into the ultimate cause of AD, and to prove that any drug target is valuable in AD, disease-relevant models giving insight into the pathogenic processes in AD are urgently needed. In the absence of a good animal model for sporadic AD, we propose in this review that induced pluripotent stem cells, derived from dermal fibroblasts of AD patients, and differentiated into cholinergic neurons, might be a promising novel tool for disease modelling and drug discovery for the sporadic form of AD.

Keywords

Stem cells Cell culture model Alzheimer’s disease Drug discovery 

Notes

Acknowledgments

We thank Peter Riederer for his brilliant scientific ideas and valuable mentorship in his long and distinguished scientific career. We gratefully acknowledge the grant support of the National Health and Medical Research Council (Grant IDs: 436797, 606543, 1046227) and Alzheimer’s Australia.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Lezanne Ooi
    • 1
  • Kuldip Sidhu
    • 6
  • Anne Poljak
    • 2
  • Greg Sutherland
    • 7
  • Michael D. O’Connor
    • 3
    • 4
  • Perminder Sachdev
    • 5
  • Gerald Münch
    • 1
    • 4
    Email author
  1. 1.Department of Pharmacology, School of MedicineUniversity of Western SydneyPenrith South DCAustralia
  2. 2.Bioanalytical Mass Spectrometry FacilityUniversity of New South WalesKensingtonAustralia
  3. 3.Regenerative Medicine, School of MedicineUniversity of Western SydneyCampbelltownAustralia
  4. 4.Molecular Medicine Research GroupUniversity of Western SydneyCampbelltownAustralia
  5. 5.Brain and Ageing Research Program, School of PsychiatryUniversity of New South WalesSydneyAustralia
  6. 6.Stem Cell Laboratory, Faculty of MedicineUniversity of New South WalesSydneyAustralia
  7. 7.Discipline of Pathology, School of Medical SciencesUniversity of SydneySydneyAustralia

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