A gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI. And when a person has certain variants of both FTO and a recognized Alzheimer's risk gene known as APOE, the risk of Alzheimer's could be doubled.
"While scientists know Alzheimer's involves progressive brain cell failure, they have not yet identified any single reason why cells fail," said Maria Carrillo, PhD, senior director of Medical and Scientific Relations at the Alzheimer's Association. "However, there is evidence about certain factors that may increase the likelihood of developing Alzheimer's."
"Some of these factors we can't control, such as age, family history, and genetics," Carrillo said. "Others we may be able to influence, including heart health, tobacco and alcohol use, and head injury."
FTO has previously been shown to affect body mass index (BMI), leptin levels (a protein hormone that plays a key role in appetite and metabolism), and the risk for diabetes. These vascular risk factors have also been associated with risk of Alzheimer's disease.
In the study reported at AAICAD 2010, Caroline Graff, MD, PhD, and colleagues at the Karolinska Institutet, Sweden, explored the direct role of the FTO gene on Alzheimer's and dementia risk in old age. In addition, a possible interaction of FTO with the APOE gene, a well-established genetic risk factor for Alzheimer's, was assessed. The researchers followed 1,003 people aged 75 years and older without dementia from the Kungsholmen project, Sweden, for nine years to detect new cases of Alzheimer's and dementia. All participants had been genotyped for FTO and APOE on DNA sampled at the beginning of the study.
They found that people in the study population who carried the AA gene-variant in the FTO gene had a 58 percent increased risk for developing Alzheimer's and a 48 percent increased risk for developing dementia compared with those who did not have this genetic variant, after adjustment for age, gender, education, and APOE genotype.
The findings also suggest that the risk-effect of FTO-AA on dementia is further elevated to 100 percent increased risk in the presence of APOE epsilon4, which is the highest risk variant of the APOE gene. The effect of the FTO-AA genotype on Alzheimer's and dementia risk remained after additional adjustment for diabetes, BMI, cardiovascular disease and physical inactivity.
"One of the intriguing aspects of the results is that the increased risk was independent of the traits previously associated with FTO, such as obesity and diabetes measured at baseline," Graff said. "Our results suggest that the mechanism by which FTO is associated with an increased risk for Alzheimer's and dementia may be different from how it increases the risk for obesity."
"This is a fascinating early finding, which fits with the known connections between heart health and brain health," Carrillo said. "However we do need to see these results confirmed by other researchers. In fact, we desperately need to know more, in general, about the genetics and other causes of Alzheimer's so that we have additional targets for therapies and preventions. One major positive step in that direction would be for the federal government to address its chronic underfunding of Alzheimer's disease research."
The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
About the Alzheimer's Association
The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800-272-3900.
--Caroline Graff, et al. The obesity related gene, FTO, increases the risk for incident Alzheimer disease in a prospective population based study. (Funded by: Swedish Brain Power Initiative, Karolinska Institutet's Faculty funding for postgraduate students, Swedish Research Council in Medicine, Forskningsradet for Arbetsliv och Socialvetenskap (Sweden), Anslag forskning och utveckling (FAS, Stockholms lans landsting), the Gun & Bertil Stohne's Foundation, Marianne and Marcus Wallenberg Foundation, Swedish Alzheimer Foundation, Gamla tjanarinnor Foundation.)
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Bob DeMarco is the editor of the Alzheimer's Reading Room and an Alzheimer's caregiver. Bob has written more than 1,610 articles with more than 8,000 links on the Internet. Bob resides in Delray Beach, FL.
Original content Bob DeMarco, the Alzheimer's Reading Room