This review examined brain tissue from people with autism spectrum disorder to understand how immune cells called microglia function in these brains. The researchers looked at data from human postmortem studies, bulk transcriptomics, single-cell atlases, and in vivo neuroimmune imaging. They found that immune and glia-associated alterations were present in at least a subset of these brains. However, the findings do not support a single microglial phenotype that applies to all cases of autism. Instead, the evidence is more consistent with variation that depends on the brain region, developmental stage, sex, and specific context.
The review highlights that much of the detailed mechanistic literature on immunometabolism currently derives from aging and neurodegeneration. This creates a challenge for researchers trying to distinguish primary pathogenic effects from secondary adaptation in autism. The main reason to be careful is that molecular signatures must be related to specific synaptic remodeling rather than just non-specific inflammatory labels.
Readers should take from this that the literature supports a more precise interpretation of microglial biology based on developmental timing and cellular context. Current evidence suggests we need to look at mechanism-linked readouts instead of assuming a single inflammatory cause for all autism cases. The study notes that much of the detailed mechanistic immunometabolism literature still derives from aging and neurodegeneration, which complicates direct comparisons. Overall, the review calls for careful interpretation of how these cells function in different parts of the brain and at different ages.
