Researchers have identified fourteen genes that could be implicated in Alzheimer's disease, and one gene in particular shows the importance that inflammation may play in the brain of Alzheimer's patients.
The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) produced stem cells and neural precursor cells (NPCs), representing early neural progenitor cells that build the brain, from patients with severe early-onset AD with mutations in the Presenilin 1 (PSEN1) gene. These NPCs had elevated Abeta42/Abeta40 ratios, indicating elevation of the form of amyloid found in the brains of Alzheimer's patients. These levels were greater than those in adult cells that did not have the PSEN1mutation.
This elevated ratio showed that these NPCs grown in the petri dish were accurately reflecting the cells in the brains of FAD patients.
Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation, said that these genes provide them with new targets to help elucidate the cause of sporadic forms of the disease as well provide targets for the discovery of new drugs.
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.
The study has been published in PLOS ONE.
