The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for 
AD are advancing age and diabetes. Lately, obesity has been associated with an 
increased risk of dementia. Obese and diabetic individuals are prone to 
decreased circulating levels of zinc, reducing the amount of zinc available for 
crucial intracellular processes. In the brain, zinc co-localizes with glutamate 
in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc 
is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect 
modulation of intracellular signaling. The ZNT and ZIP proteins participate in 
intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins 
has been described in AD patients. Using microarray data from human frontal 
cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and 
SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 
145 neurologically and psychiatrically normal individuals. Expression of ZNT3 
and ZNT4 were significantly reduced with increasing age, whereas expression of 
ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index 
(BMI) correlated with a significant reduction in ZNT1 expression similar to what 
is seen in the early stages of AD. Increasing BMI also correlated with reduced 
expression of ZNT6. In conclusion, we found that the expression of genes that 
regulate intracellular zinc homeostasis in the human frontal cortex is altered 
with increasing age and affected by increasing BMI. With the increasing rates of 
obesity throughout the world, these findings warrant continuous scrutiny of the 
long-term consequences of obesity on brain function and the development of 
neurodegenerative diseases.