Researchers led by Takeo Yoshikawa from the RIKEN Center for Brain Research in Japan have discovered a biomarker that can detect autism spectrum disorder (ASD) in preschool children. Published in Brain communicationThe new study found that levels of the FABP4 protein in four- to six-year-old children with ASD were much lower than other typically developing children. Experiments in mice lacking FABP4 showed changes in neurons similar to those in the post-mortem brain of people with ASD.
ASD is a developmental disorder that begins in early childhood and affects learning, communication, and social behavior. Symptom severity falls across a wide range that researchers believe may be related to genetic and environmental factors that interact during brain development. Since young children with ASD are at a particular risk of obesity, the RIKEN CBS group suspected a link between ASD and fat cell metabolism.
Fat cells make hundreds of important biomolecules called adipokines, some of which regulate brain activity. The researchers took blood samples from preschoolers with and without ASD and compared their adipokine levels. The team looked at adipokines known to be associated with ASD and the protein FABP4. “We previously found lower FABP4 levels in the hair follicles of patients with schizophrenia,” explains first author Motoko Maekawa. “Although the disorders themselves vary widely, we knew that FABP4 is an adipokine that can modulate brain function, particularly during development.”
The researchers found that preschoolers with ASD had much less FABP4 in their blood than other children, but other adipokines did not differ between groups. A second test in two other groups of children confirmed these results. This makes FABP4 a potential early biomarker for ASD. “The identification of FABP4 as a biomarker that can detect ASD in children ages four to six is good news,” says Maekawa, “especially because early diagnosis and intervention can lead to better long-term prognosis.”
Further analysis showed that the story is a little more complex. Similar comparisons in older children and in post-mortem brains showed equal FABP4 levels between ASD and non-ASD groups. This means that FABP4 levels differ during a critical period during brain development, making it more than just a biomarker. Its deficiency could be a factor leading to the disease rather than just a by-product.
To confirm the importance of FABP4, the researchers developed knockout mice that lacked the FABP4 gene. When compared to wild-type mice, behavioral tests showed that these mice interacted less with unknown mice and had greater difficulty with spatial learning and memory, reminiscent of difficulties shared by those with ASD. When the team examined the neurons in the mouse brain, they also found shape and structural features that are consistent with those in the postmortem brain of people with ASD.
Looking ahead, there are three questions the researchers want to answer. “We hope to replicate our results in a larger group to see if certain ASD symptoms or their severity are related to low FABP4 levels,” says Maekawa. “We also hope to conduct a prospective cohort study of newborns to determine whether FABP4 levels at birth can predict the future manifestation of ASD.”
Lastly, researchers will continue to study ASD’s FABP4 mouse model to understand exactly how the FABP4 protein affects the developing brain.
Reference: “A possible role for fat acid Binding Protein 4 in the Pathophysiology of Autism Spectrum Disorder “by Maekawa et al., September 10, 2020, Brain communication.
DOI: 10.1093 / braincomms / fcaa145