Researchers Model Alzheimer’s Disease From Patients’ Skin Cells

Japanese researchers have grown cortical neurons and astrocytes using fibroblasts from Alzheimer’s disease patients.

AsianScientist (Feb. 25, 2013) – Japanese researchers have grown cortical neurons and astrocytes using fibroblasts from Alzheimer’s disease (AD) patients.

The Cell Stem Cell study was a collaboration between Associate Professor Haruhisa Inoue’s lab at the Center for iPS Cell Research and Application (CiRA) at Kyoto University and Professor Nobuhisa Iwata’s lab at Nagasaki University.

In the study, the researchers differentiated cortical neurons and astrocytes using induced pluripotent stem cells (iPSCs) derived from two familial AD patients with mutations in amyloid precursor protein (APP), and two sporadic AD patients.

The iPSC-derived neurons showed characteristics of neurons found in AD patients. Cells 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 (ABeta) oligomers.

The team found that these stress phenotypes could be reduced with docosahexaenoic acid (DHA), an omega-3 fatty acid identified as a potential treatment for AD. 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.

Disease progression also 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. “Further advances in iPSC technology will be required before large-scale analysis of AD patient-specific iPSCs is possible.”

The article can be found at: Kondo T et al. (2013) Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβ and Differential Drug Responsiveness.


Source: CiRA; Photo: Dr. Haruhisa Inoue’s laboratory.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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