Autism spectrum disorders (ASD) affect a growing number of people, but their biological causes remain largely unknown. The heterogeneity of ASD manifestations makes it difficult to develop effective treatments, as universal approaches have shown their limitations. Fragile X syndrome, a genetic mutation that is the leading hereditary cause of ASD, is a valuable model for better understanding certain common mechanisms. It is in this context that Dr. Artuela Çaku, a biochemist specializing in lipidology at Centre de recherche mère-enfant du CHU de Sherbrooke, became interested in the role of cholesterol. In clinical studies, her team observed that nearly 30% of people with Fragile X syndrome—and a similar proportion of people with autism—had abnormally low cholesterol levels. Cholesterol is a molecule that is essential for the development and proper functioning of the brain.
Dr. Çaku’s research has revealed a link between low blood cholesterol levels and certain cognitive and behavioral traits (hyperactivity, stereotypical movements, or language disorders). Since the brain produces its own cholesterol independently of the rest of the body, the team sought to determine whether these peripheral abnormalities also reflected what was happening in the brain. To do this, they developed innovative methods for measuring cholesterol metabolites from the brain, called “oxysterols,” from a blood sample. The results show, in particular, a decrease in 24-hydroxycholesterol, a key marker of brain cholesterol metabolism. At the same time, collaborations with the Institut de recherche clinique de Montréal have identified an alteration in the PCSK9 protein, which is involved in cholesterol regulation, offering a possible explanation for these observations.
This work paves the way for a personalized medical approach to autism. By identifying a subgroup of people with ASD who have specific abnormalities in cholesterol metabolism, it becomes possible to consider more refined screening tools and, ultimately, more tailored interventions.
References
Çaku, A., Seidah, N. G., Lortie, A., Gagné, N., Perron, P., Dubé, J., & Corbin, F. (2017). New insights of altered lipid profile in fragile X Syndrome. PLoS One, 12(3):e0174301. https://doi.org/10.1371/journal.pone.0174301
Laroui, A., Rojas, D., Bouhour, S., Proteau-Lemieux, M., Galarneau, L., Benachenhou, S., Abolghasemi, A., Plantefeve, R., Mallet, P.-L., Corbin, F., Lepage, J.-F., & Çaku, A. (2025). Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome. Journal of Lipid Research, 66(5), 100787. https://doi.org/10.1016/j.jlr.2025.100787