Modeling Alzheimer's disease using iPSCs

February 21, 2013, Kyoto University
This shows amyloid beta oligomers in neurons from a familial AD (APP-E693 delta) (left) and from a sporadic AD patient (right). Credit: Courtesy of Dr. Haruhisa Inoue's laboratory

Working with a group from Nagasaki University, a research group at the Center for iPS Cell Research and Application (CiRA) at Japan's Kyoto University has announced in the Feb. 21 online publication of Cell Stem Cell has successfully modeled Alzheimer's disease (AD) using both familial and sporadic patient-derived induced pluripotent stem cells (iPSCs), and revealed stress phenotypes and differential drug responsiveness associated with intracellular amyloid beta oligomers in AD neurons and astrocytes.

In a study published online in Cell Stem Cell, Associate Professor Haruhisa Inoue and his team at CiRA and a research group led by Professor Nobuhisa Iwata of Nagasaki University generated and from iPSCs derived from two familial AD patients with mutations in amyloid (APP), and two sporadic AD patients. The from one of the familial and one of the sporadic patients showed endoplasmic reticulum (ER)-stress and oxidative-stress phenotypes associated with intracellular amyloid beta oligomers. The team also found that these stress phenotypes were attenuated with docosahexaenoic acid (DHA) treatment. These findings may help explain the variable clinical results obtained using DHA treatment, and suggest that DHA may in fact be effective only for a subset of patients.

Using both familial and sporadic AD iPSCs, the researchers discovered that pathogenesis differed between individual AD patients. For example, secreted amyloid beta 42 levels were depressed in familial AD with APP E693 delta mutation, elevated in familial AD with APP V717L mutation, but normal in sporadic AD.

"This shows that patient classification by iPSC technology may contribute to a preemptive therapeutic approach toward AD,'' said Inoue, a principal investigator at CiRA who is also a research director for the CREST research program funded by the Japan Science and Technology Agency. "Further advances in iPSC technology will be required before large-scale analysis of AD patient-specific iPSCs is possible.''

Explore further: A drug-screening platform for ALS

More information: Kondo et al. "Modeling Alzheimer's disease using iPSCs reveals stress phenotypes associated with intracellular amyloid beta and differential drug responsiveness.''

Related Stories

A drug-screening platform for ALS

August 2, 2012
A research group at the Center for iPS Cell Research and Application (CiRA) at Japan's Kyoto University has successfully recapitulated amyotrophic lateral sclerosis (ALS)-associated abnormalities in motor neurons differentiated ...

Alzheimer's neurons induced from pluripotent stem cells

January 25, 2012
Led by researchers at the University of California, San Diego School of Medicine, scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease (AD), using ...

Bypassing stem cells, scientists make neurons directly from human skin

August 4, 2011
Researchers have come up with a recipe for making functional neurons directly from human skin cells, including those taken from patients with Alzheimer's disease. The new method may offer a critical short cut for generating ...

Recommended for you

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...

Molecular mechanism behind HIV-associated dementia revealed

January 5, 2018
For the first time, scientists have identified and inhibited a molecular process that can lead to neurodegeneration in patients with HIV, according to a Northwestern Medicine study published in Nature Communications.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.