Fibroblast growth factor23 is associated with axonal integrity and neural network architecture in the human frontal lobes.

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2018-01

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Marebwa, Barbara K
Adams, Robert J
Magwood, Gayenell S
Kindy, Mark
Wilmskoetter, Janina
Wolf, Myles
Bonilha, Leonardo

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Abstract

Elevated levels of FGF23 in individuals with chronic kidney disease (CKD) are associated with adverse health outcomes, such as increased mortality, large vessel disease, and reduced white matter volume, cardiovascular and cerebrovascular events. Apart from the well-known link between cardiovascular (CV) risk factors, especially diabetes and hypertension, and cerebrovascular damage, elevated FGF23 is also postulated to be associated with cerebrovascular damage independently of CKD. Elevated FGF23 predisposes to vascular calcification and is associated with vascular stiffness and endothelial dysfunction in the general population with normal renal function. These factors may lead to microangiopathic changes in the brain, cumulative ischemia, and eventually to the loss of white matter fibers. The relationship between FGF23 and brain integrity in individuals without CKD has hitherto not been investigated. In this study, we aimed to determine the association between FGF23, and white matter integrity in a cohort of 50 participants with varying degrees of CV risk burden, using high resolution structural human brain connectomes constructed from MRI diffusion images. We observed that increased FGF23 was associated with axonal loss in the frontal lobe, leading to a fragmentation of white matter network organization. This study provides the first description of the relationship between elevated levels of FGF23, white matter integrity, and brain health. We suggest a synergistic interaction of CV risk factors and FGF23 as a potentially novel determinant of brain health.

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10.1371/journal.pone.0203460

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Marebwa, Barbara K, Robert J Adams, Gayenell S Magwood, Mark Kindy, Janina Wilmskoetter, Myles Wolf and Leonardo Bonilha (2018). Fibroblast growth factor23 is associated with axonal integrity and neural network architecture in the human frontal lobes. PloS one, 13(9). p. e0203460. 10.1371/journal.pone.0203460 Retrieved from https://hdl.handle.net/10161/18490.

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Wolf

Myles Selig Wolf

Charles Johnson, M.D. Distinguished Professor of Medicine

The focus of my research is disordered mineral metabolism across the spectrum of chronic kidney disease, including dialysis, kidney transplantation and earlier stages.

My research has been published in leading general medicine and subspecialty journals, including the New England Journal of Medicine, JAMA, the Journal of Clinical Investigation, Circulation, Cell Metabolism, Journal of the American Society of Nephrology, and Kidney International, among others.

My primary contributions have been in the area of hormonal regulation of phosphate homeostasis. I have helped to characterize the physiological role of fibroblast growth factor 23 in health and in chronic kidney disease, and the impact of elevated fibroblast growth factor 23 levels on adverse clinical outcomes in patients with kidney disease.


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