First observations of a potential association between accumulation of per- and polyfluoroalkyl substances in the central nervous system and markers of Alzheimer's disease

By Nicolas Delcourt, Alix-Marie Pouget, Alicia Grivaud, Leonor Nogueira, Frédéric Larvor, Philippe Marchand, Eric Schmidt, and Bruno Le Bizec
J Gerontol A Biol Sci Med Sci
August 31, 2023
DOI: 10.1093/gerona/glad208

The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from eight patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate (PFOS) were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and PFOS in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared to those with only one or neither. Two previous studies have shown that PFAS levels in Human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide a first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.

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