Several theories exist as to the etiology of dementia. One of these is that aluminum is somehow involved as a causal agent. Another is that, for some reason, patients with dementia have a defective blood-brain barrier that allows neurotoxins (such as aluminum) access to the brain. We have recently published evidence showing that aluminum itself can induce an increase in the permeability of the blood-brain barrier to behaviorally potent neuropeptides. Such an action could be the mechanism by which aluminum leads to dementia. The purpose of the studies proposed here is to look for possible mechanisms by which aluminum could induce increased blood-brain barrier permeability. The elucidation of such mechanisms is the first step in the application of this new knowledge in developing future treatments for dementia. Briefly, the chief mechanisms that will be investigated include looking at the effect that aluminum has on blood flow to the brain, on brain transport mechanisms (such as active transport and bulk flow), and on blood and brain levels of inorganic phosphorus and cholinesterase. The effect of aluminum on the transport of neuropeptides not previously investigated as well as nonpeptide substances will also be studied. The information obtained will greatly enhance our understanding of aluminum's effect on the blood-brain barrier and its role in dementias. Such an understanding is crucial to the development of specific treatments for dementia.
