PFASs May Risk Alzheimer’s Disease

We are now living in an aging society with increasingly older population, many of whom are suffering with or are at a high risk of developing dementia (1,2). Alzheimer’s disease (AD) is the world’s most common type of dementia, affecting about 50 million individuals worldwide currently, with that number set to rise to 82 million by 2023. There is a huge challenge in developing an anti-AD drug, and an enormous amount of effort has been devoted to this branch of research. It is encouraging that the 2 recently described anti-Aβ antibodies, lecanemab and donanemab, show clear benefits in slowing cognitive decline in patients with early-stage disease; however, rare but severe side effects (such as brain bleeding and swelling) still occur (10.1126/science.adj8110), indicating that there is likely a longway to go in developing a cure for AD (3,4).Although the hunt is on to develop an anti-AD drug to stop disease progression, it is also important and necessary to focus on prevention. It has been reported that lifestyle patterns and environmental toxins (natural and anthropogenic) increase the risk of dementia, with some estimates noting up to a 30% increase in AD risk. These factors are modifiable and reducing such risks could prevent or slow down the onset of dementia (5,6). Environmental toxins cover a broad spectrum of chemicals, including pesticides (organochlorine and organophosphate insecticides), toxic metals (such as aluminum), air pollutants, and especially industrial chemicals (6). Although we are exposed to trace amount of these contaminants during our daily lives, a lifelong accumulation could presumably reach to a toxic level, jeopardizing neuronal function and brain health.Per- and polyfluoroalkyl substances (PFASs) are a group of man-made chemicals that have been widely used in consumer products around the world since the 1950s. They have been very widely used and closely linked to our daily lives, being used, for example, on fabrics to provide stain resistance, and on cookware to keep food from sticking to it. While PFAS compounds facilitate our lives, they have brought environmental challenges with them, mainly due to their broad application, vast numbers (there are thousands of fluoroalkyl chemical compounds), and due to a chain of linked carbon and fluorine atoms that result in very slow breakdown over time, a long lifespan (7). Due to its widespread use, humans have been widely exposed to these chemicals, many of which can now be found in blood and cerebrospinal fluid (CSF) samples. In combination with data from laboratory animals, it is suggested these chemicals may cause a series of health issues, as summarized in Figure 1 (7,8).In this issue, Delcourt and colleagues (9) present a small human study showing patients with high CSF PFASs correlate with AD. Here, using the CSF samples from 8 patients hospitalized with suspected normal pressure hydrocephalus, they checked levels of 18 of the most common PFAS molecules. PFASs were detected in all 8 CSF samples, and a correlation was seen between high PFOS (perfluorooctane sulfonate) and cognitive impairment among the tested individuals. This discovery brings with it a sense of urgency in reducing exposure to PFASs in our daily lives and highlights the risks that it may bring in terms of our brain health. As this is a small-size proof-of-concept study, further large-size clinical validation and underlying molecular investigation are needed.E.F.F. is supported by Cure Alzheimer’s Fund (#282952), HELSE SØR-ØST (#2020001, #2021021, #2023093), the Research Council of Norway (#262175, #334361), Molecule AG/VITADAO (#282942), NordForsk Foundation (#119986), the National Natural Science Foundation of China (#81971327), Akershus University Hospital (#269901, #261973, #262960), the Civitan Norges Forskningsfond for Alzheimers sykdom (#281931), the Czech Republic-Norway KAPPA programme (with Martin Vyhnálek, #TO01000215), the Rosa sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society (#207819), and Wellcome Leap (#104617).E.F.F. is the co-owner of Fang-S Consultation AS (Organization number 931 410 717); he has an MTA with LMITO Therapeutics Inc. (South Korea), a CRADA arrangement with ChromaDex (United States), a commercialization agreement with Molecule AG/VITADAO; he is a consultant to Aladdin Healthcare Technologies (United Kingdom and Germany), the Vancouver Dementia Prevention Centre (Canada), Intellectual Labs (Norway), MindRank AI (China), and NYO3 (Norway and China). H-L.W. declares no conflict of interest.