Stem cell research identifies new gene targets in patients with Alzheimer’s disease

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 8, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) 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.

In this study, published today in PLOS ONE, the team of scientists 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.

"Our ability to accurately recapitulate the disease in the petri dish is an important advance for this disease. These genes provide us with new targets to help elucidate the cause of sporadic forms of the disease as well provide targets for the discovery of new drugs," said Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation.

"The gene expression profile from Noggle's familial Alzheimer's stem cells points to inflammation which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene. The greatest breakthroughs come with 'unknown unknowns', that is, things that we don't know now and that we would never discover through standard logic," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimer's Disease Research Center.

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.

Although the majority of Alzheimer's disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimer's disease and are one hundred percent 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.

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Stem cell research identifies new gene targets in patients with Alzheimer's disease

Breakthrough Research Provides Valuable Insight On Cause Of Alzheimer’s

New York, NY (PRWEB) January 08, 2014

A stem cell model of familial Alzheimers disease (FAD) was successfully generated, allowing researchers to identify 14 genes potentially implicated in the disease. One gene in particular demonstrates the important role inflammation may play in the brain of Alzheimers patients. The study was completed by scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) and funded in part by the Cure Alzheimers Fund(CAF).

In the study published today in PLOS ONE, a team of scientists 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 Alzheimers patients. These levels were greater than those in adult cells that did not have the PSEN1 mutation. This elevated ratio shows that the NPCs grown in the petri dish accurately reflected the cells in the brains of FAD patients.

"The gene expression profile from the familial Alzheimers stem cells points to inflammation, which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimers Disease Research Center and leader of the Cure Alzheimers Fund Stem Cell Consortium.

"This is the kind of innovative science that will help us better understand the cause of Alzheimers and how to approach the disease with effective therapies," said Tim Armour, President and CEO of Cure Alzheimers Fund (CAF). "It also showcases how targeted investment of critical resources can make a difference in finding solutions to this debilitating disease."

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 14 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 Alzheimers disease patients brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimers disease.

The studys co-lead authors Sam Gandy, MD, PhD and Scott Noggle, PhD are both members of CAFs Stem Cell Consortium, which supported this research. The Stem Cell Consortium is an international group of scientists collaborating on innovative research that investigates, for the first time, the brain cells from individuals with the common form of Alzheimers disease. Other members of the Consortium include Kevin Eggan, PhD, of Harvard University, Marc Tessier-Lavigne, PhD, of Rockefeller University, Doo Kim, PhD, of Harvard Medical School, and Tamir Ben-Hur, MD, PhD, of Hadassah University.

Stem cells are the least mature cells in the body. This means they can be treated with a defined cocktail of factors that can cause maturation of cells along discrete cell types. With iPS cells, which are cells that can become any cell type in the body, it now is possible to take skin cells from adults and return them to an immature state. By redirecting skin cells from Alzheimers patients and turning them into nerve cells, investigators are able to study adult Alzheimers neurons (nerve cells) in the lab.

Although the majority of Alzheimers disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimers disease and are one hundred percent penetrant, resulting in all individuals with this mutation getting the disease.

Identifying genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimers disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.

Read more:
Breakthrough Research Provides Valuable Insight On Cause Of Alzheimer’s

Arizona Pain Stem Cell Institute Now Offering PRP Therapy for Joint Arthritis Relief

Phoenix, AZ (PRWEB) January 08, 2014

The top Phoenix stem cell clinic in the Valley, Arizona Pain Stem Cell Institute, is now offering PRP therapy for joint arthritis relief. Platelet rich plasma therapy offers the potential for relieving the pain from knee, hip, shoulder and spinal arthritis. For more information and scheduling with the Board Certified Phoenix pain management doctors, call (602) 507-6550.

Platelet rich plasma therapy, known as PRP therapy, involves a simple blood draw. The blood is then spun in a centrifuge, which then concentrates platelets and growth factors for immediate injection into the arthritic joint. The PRP therapy then acts as an attractant for the body's stem cells.

Recent published studies have shown that PRP therapy offers significant pain relief for arthritic knees and helps preserve existing cartilage. One to three injections may be necessary to obtain optimal results, which are performed as an outpatient and entail minimal risk.

In addition to PRP therapy, the Arizona Pain Stem Cell Institute offers several other regenerative medicine treatments for both joint and spinal arthritis. This includes bone marrow and fat derived stem cell injections along with amniotic stem cell rich injections. These injections are offered for patients as part of numerous clinical research studies.

The stem cell injection studies are enrolling now at the Institute. The studies are industry subsidized, with the procedures performed by the Board Certified pain management physicians.

The Arizona Pain Stem Cell Institute is part of Arizona Pain Specialists. With 5 locations accepting over 50 insurances, the pain clinics offer comprehensive treatment options for patients with both simple and complicated pain conditions.

Call (602) 507-6550 for more information and scheduling.

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Arizona Pain Stem Cell Institute Now Offering PRP Therapy for Joint Arthritis Relief