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Archive - 10 - 2013
Changes in Epigenetic DNA Functions Reveal How Diabetes Predisposes Individuals to Alzheimer’s Disease
Mount Sinai Researchers Hope to Exploit Findings to Develop Novel Preventive and Treatment Strategies for Alzheimer's Disease October 22, 2013 (Newswise) -- Diabetes and dementia are rising dramatically in the United States and worldwide. In the last few years, epidemiological data has accrued showing that older people with diabetes are significantly more likely to develop cognitive deterioration and increased susceptibility to onset of dementia related to Alzheimer's disease. Now, a research team led by Giulio Maria Pasinetti, MD, PhD, the Saunders Family Chair and Professor of Neurology at the Icahn School of Medicine at Mount Sinai, discovered a novel mechanism through which this may occur. The results are published online Oct. 23, in the journal Diabetes. Dr. Pasinetti and colleagues pinpointed changes in post-mortem brains of human subjects. They reported that gene expression was dysfunctional in the brains of diabetic human subjects, and this increase was associated with reduced expression of important molecules that play a critical role in maintaining the structural integrity of brain regions associated with learning. Excited by this finding, Dr. Pasinetti reasoned that if the hypothesis was correct, similar conditions should be repeated in the laboratory by inducing diabetes in mice genetically predisposed to developing Alzheimer's type memory deterioration.
In fact, Dr. Pasinetti's laboratory confirmed this prediction in the mouse model, supporting the hypothesis that diabetes, through epigenetic changes in the brain, may casually promote onset and progression of Alzheimer's disease. Epigenetic changes are chemical changes in DNA that effect gene expression, but don't alter the actual genetic code. "This new evidence is extremely intriguing, given that approximately 60 percent of Alzheimer's disease patients have at least one serious medical condition associated with diabetes," said Dr. Pasinetti. "What this adds is much needed insight into the potential mechanism that might explain the relationship between diabetes and Alzheimer's disease onset and progression by mechanisms through which DNA functions." The discovery in Dr. Pasinetti's laboratory has staggering societal implications. More than 5 million are affected by Alzheimer's disease dementia, and the disease incidence is expected to skyrocket in the three decades as the population ages. "The next question we must ask is how we can translate this into the development of novel disease prevention and treatment strategies," Dr. Pasinetti added. "If we can find out how DNA epigenetic modification can be manipulated pharmacologically, these studies will be instrumental in the formulation of novel treatments and possible preventative strategies in Alzheimer's disease. Collaborating on this research were several people, also at the Icahn School of Medicine at Mount Sinai: Tuyen Nguyen, PhD, Weina Bi, BA, Amanda Bilski, BA, Shimul Begum, BA, Preshant Vempati, MS, Lindsay Knable BA, and Lap Ho, PhD. About the Passinetti Laboratory
The primary research goals in Dr. Pasinetti's laboratory are to investigate the biological processes which occur when, during aging, subjects with normal cognitive functions convert into the very earliest stages of Alzheimer's disease (AD) and then to frank dementia. Dr. Pasinetti's lab is presently using newly developed transgenic mouse models genetically modified to develop disease to test pre-clinically the potential therapeutic relevance of novel drug treatments to be further developed in clinical application. About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services?from community-based facilities to tertiary and quaternary care.
The System includes approximately 6600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.
October 22, 2013 (Healio) -- Patients with diabetes- and steatohepatitis-related liver disease are more likely to develop hepatocellular carcinoma, cirrhosis and encephalopathy ? and at a faster rate ? than nondiabetic patients, a presenter said here. "Diabetes is proving to be a much more important risk factor for ? not just nonalcoholic steatohepatitis ? but alcoholic steatohepatitis and the development of the disease process," Evan Raff, MD, of the department of internal medicine at the University of Alabama at Birmingham, said during the American College of Gastroenterology Annual Scientific Meeting. "It's proving to increase the likelihood of worsening of the disease from simple inflammation to fibrosis and, eventually, hepatocellular carcinoma formation." Researchers analyzed 503 medical charts of patients with steatohepatitis-related liver disease for demographics, comorbidities including diabetes mellitus, cirrhosis and complications, hepatocellular carcinoma and laboratory, imaging, and histology data, Raff said. Diabetic patients (n=206) more often presented with cirrhosis (75% vs. 64%; P=.01) and hepatocellular carcinoma (9% vs. 3%; P=.005) than nondiabetic patients (n=297), he said. They also were more likely to develop hepatic encephalopathy (31% vs. 19%; P=.003) with a trend for higher stage 3 or 4 fibrosis in 95 biopsied cases (67% vs. 49%; P=.09) than patients without diabetes. Diabetes mellitus also independently predicted the presence of cirrhosis and hepatocellular carcinoma. "Increased screening methods may need to be imposed as a result of these finding," Raff said. "If you know somebody has diabetes and you know they also have some form of steatohepatitis ? they may require different screening modalities and surveillance guidelines for things like hepatocellular carcinoma or earlier interventions for their liver disease."