Fluoride and Alzheimer's (linked from Hampel paper just posted):
Int J Mol Sci. 2018 Dec; 19(12): 3965. Published online 2018 Dec 9. doi: 10.3390/ijms19123965 PMCID: PMC6320968 PMID: 30544885 Potential Role of Fluoride in the Etiopathogenesis of Alzheimer’s Disease Marta Goschorska,1,* Irena Baranowska-Bosiacka,1 Izabela Gutowska,2 Emilia Metryka,1 Marta Skórka-Majewicz,2 and Dariusz Chlubek1 Author information Article notes Copyright and License information Disclaimer Go to: Abstract The etiopathogenesis of Alzheimer’s disease has not been fully explained. Now, the disease is widely attributed both to genetic and environmental factors. It is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants. Fluoride is widespread in the environment and it easily crosses the blood–brain barrier. In the brain fluoride affects cellular energy metabolism, synthesis of inflammatory factors, neurotransmitter metabolism, microglial activation, and the expression of proteins involved in neuronal maturation. Finally, and of specific importance to its role in Alzheimer’s disease, studies report fluoride-induced apoptosis and inflammation within the central nervous system. This review attempts to elucidate the potential relationship between the effects of fluoride exposure and the pathogenesis of Alzheimer’s disease. We describe the impact of fluoride-induced oxidative stress and inflammation in the pathogenesis of AD and demonstrate a role for apoptosis in disease progression, as well as a mechanism for its initiation by fluoride. The influence of fluoride on processes of AD initiation and progression is complex and warrants further investigation, especially considering growing environmental fluoride pollution.
Keywords: Alzheimer’s disease, fluoride, neuroinflammation, reactive oxygen species, cyclooxygenases, antioxidant enzymes, apoptosis Go to: 1. Introduction Alzheimer’s disease (AD) is a progressive, irreversible neurodegenerative disease and one of the most common causes of dementia. Its clinical symptoms, including the impairment of memory and cognitive functions, are caused by neuronal loss, primarily in the hippocampus and neocortex [1]. Characteristic pathomorphological signs of Alzheimer’s disease include neurofibrillary tangles (NFTs) and amyloid plaques (AßPs), also known as senile plaques. Additionally, pathomorphological studies on AD brains reveal the presence of amyloid neuropathy, granulovacuolar degeneration, synaptic pathology, white matter rarefaction, transactive response DNA-binding protein 43 (TDP-43) pathology, and neuroinflammation [2,3].
Although the etiopathogenesis of AD has not been fully explained, a distinction has been made between its sporadic (sAD) and familial forms (fAD), and the disease is now widely attributed both to genetic and environmental factors [4].
Go to: 2. The Role of Environmental Factors in AD Etiopathogenesis At present, it is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants [5]. Studies of AD risk factors have been largely inconclusive; however, they have succeeded in generating a list of potential risk factors and demonstrating that the role of these environmental factors in the development of AD is equally important as that of previously established associated genetic mutations [5,6]. Like other neurodegenerative diseases, risk factors include hypertension, hyperhomocysteinemia, hyperlipidemia, and exposure to pesticides and certain metal ions. Additionally, growing attention has highlighted the combination of certain factors. For example, high-fat/high energy diets have been shown to lead to increased aluminum (Al) concentrations in plasma and result in increased concentrations in the brain due to the ability of Al to cross the blood–brain barrier (BBB) [6]. Al has also been shown to alter BBB functions, increasing permeability for nonmetals, such as fluoride [7]. Furthermore, fluoride is known to spontaneously form complexes with trace quantities of aluminum in aqueous environments [8,9]. The roles of Al and F, mainly as AlFx and NaF, have been the subject of extensive investigation in the etiopathogenesis of AD and other human and animal diseases [8,10].
