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New Gene Target for Alzheimer’s Disease Identified

Posted Jan 20 2014 10:08pm
Posted on Jan. 20, 2014, 6 a.m. in Alzheimer's Disease Genetics in Disease Stem Cell
New Gene Target for Alzheimer’s Disease Identified

Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute (New York, USA), in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (New York, USA), successfully generated a stem cell model of familial Alzheimer's disease (FAD). Using this stem cell model, researchers identified fourteen genes that may be implicated in the disease and one gene in particular that shows the importance that inflammation may play in the brain of Alzheimer's patients.  The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations. After thorough characterization of the NPCs through gene expression profiling and other methods, they identified fourteen genes that behaved differently in PSEN1 NPCs relative to NPCs from individuals without the mutation. Five of these targets also showed differential expression in late onset Alzheimer's disease patients' brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimer's disease. PSEN1 mutations cause the most common form of inherited familial Alzheimer's disease and are one 100% penetrant, resulting in all individuals with this mutation getting the disease. The identification of genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimer's disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.  The study authors submit that their model has “have reconstituted an essential feature in the molecular pathogenesis of [familial Alzheimer's disease], increased generation of [amyloid  plaques], and have characterized novel expression changes.”

Andrew A. Sproul, Samson Jacob, Deborah Pre, Soong Ho Kim, Sam Gandy, Scott A. Noggle, et al.  "Characterization and Molecular Profiling of PSEN1 Familial Alzheimer's Disease iPSC-Derived Neural Progenitors.”  PLOS ONE, 8 Jan 2014.

  
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