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2008 Grants - Crivello
Folate Deficiency, Brain Lipids and Amyloid Toxicity in APP/PS1 Mice
Natalia A. Crivello, Ph.D.
2008 New Investigator Research Grant
Several risk factors for Alzheimer's disease have been identified, including genetic, environmental and dietary factors. One dietary factor that is receiving attention is folate, a nutrient that is essential for numerous biological functions. Indeed, several studies have reported that folate deficiency increases the brain toxicity of beta-amyloid, a protein fragment that is a leading suspect in the development of Alzheimer's disease.
When blood folate levels are low, levels of another nutrient, choline, can become depleted. Choline is essential for maintaining the structure of cell membranes and for the synthesis of some neurotransmitters, chemicals that mediate signaling between nerve cells in the brain. This effect may explain some of the detrimental effects of a folate-deficient diet.
Natalia A. Crivello, Ph.D., and colleagues are studying how dietary folate affects choline levels and amyloid toxicity in the brain. For these studies, they use mice that have been genetically altered to express high levels of beta-amyloid, which leads to an Alzheimer-like pathology. The researchers have already observed that folate deficiency leads to brain damage and cognitive impairment in these mice. They also found that folate deficiency caused choline depletion in the brain.
Dr. Crivello and colleagues plan to extend their studies of folate by examining how folate deficiency affects choline metabolism and beta-amyloid accumulation in the brains of mice at different ages. They also plan to examine different brain regions to determine whether folate deficiency affects some regions more than others. These studies will probe the biochemical mechanisms of how diet influences an individual's risk of cognitive decline and Alzheimer's disease.