Mechanisms of neurotoxicity of fluoride or aluminum: implications for neurodegenerative disease risk.

Fluoride and aluminum are two naturally abundant elements with widespread industrial uses. Fluoride is also added to community water supplies as a public health intervention for dental cavity prevention. However, findings from animal studies show potential links of fluoride and aluminum exposure with neurodegenerative disease risk, particularly at high exposure levels. This review uniquely examines neurochemical and neurobiological impacts of fluoride and aluminum exposure as well as whether these processes may increase the risk of common and rare neurodegenerative diseases, including dementia, Parkinson's Disease, and motor neuron disease. Fluoride and aluminum can cross the blood-brain barrier and accumulate in neural tissue, where they can interact to produce neurotoxic effects. Chronic exposure to fluoride and aluminum can cause oxidative stress, mitochondrial dysfunction, brain inflammation, and disruption of essential ions. These effects can contribute to impaired nerve signaling, cell damage, and protein aggregation-key factors in neurodegeneration. Co-exposure to aluminum-fluoride complexes may worsen these effects by increasing amyloid buildup and causing nerve cell death, although more research on aluminum-fluoride interactions is needed. Additionally, many animal studies include relatively high fluoride or aluminum exposure levels, and epidemiological human data are scarce, particularly for less common neurodegenerative diseases. Moreover, these studies often rely on ecological or occupational exposure measures rather than individual biomarkers. Findings of this narrative review underscore the need for methodologically rigorous longitudinal human studies on fluoride, aluminum and neurodegenerative disease risk, particularly given the mechanistic basis for these potential associations.