Alzheimer's in vitro
A model of Alzheimer's disease was created from induced pluripotent stem cells
LifeSciencesToday based on CiRA materials: Modeling Alzheimer's Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular A-beta and Differential Drug ResponsivenessIn collaboration with scientists from Nagasaki University, a research team from the Center for iPS Cell Research and Application (CiRA) of Kyoto University has successfully modeled Alzheimer's disease using induced pluripotent stem cells from patients with both familial and sporadic forms of this disease.
The researchers observed a differentiated reaction of cells to drugs and different stress phenotypes associated with intracellular amyloid beta oligomers in neurons and astrocytes.
In a study published online in the journal Cell Stem Cell (Takayuki Kondo et al., Modeling Alzheimer's Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular A-beta and Differential Drug Responsiveness), Associate Professor Haruhisa Inoue and his colleagues from CiRA and a research group led by Professor Nobuhisa Iwata from Nagasaki University obtained cortical neurons and astrocytes from iPSCs of two patients with familial form of Alzheimer's disease with mutations in the gene of amyloid precursor protein (APP) and two patients with sporadic form of this disease. Neural cells of one of the patients with familial and one of the patients with sporadic form showed phenotypes of endoplasmic reticulum stress and oxidative stress associated with intracellular amyloid beta oligomers.
In addition, scientists have found that these stress phenotypes are suppressed when cells are treated with docosahexaenoic acid (docosahexaenoic acid, DHA). These data help to explain the unstable clinical results obtained in the treatment of DHA patients, and suggest that this drug may be effective only in some patients.
After studying the iPSCs of patients with both familial and sporadic forms of Alzheimer's disease, scientists found differences in the pathogenesis of the disease. For example, secreted levels of A-beta42 were lowered in familial Alzheimer's disease with the APP E693-delta mutation, increased in familial form with the APP V717L mutation, but remained within the normal range in the sporadic form of the disease.
Beta-amyloid oligomers in neurons of a patient with familial form of Alzheimer's disease (left)
and a patient with a sporadic form of the disease. (Photo: Dr. Haruhisa Inoue's laboratory)
"This suggests that the classification of patients using iPSC–based methods can contribute to determining the priority therapeutic approach to Alzheimer's disease," says Professor Inoue. "For future large-scale analysis of Alzheimer's-specific iPSCs, further development of iPSCs technologies is necessary."
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