Are neuropsychiatric disorders caused by changes in the relative mix of brain cell types? A recent study led by Mater Researcher Dr Chloe Yap and published in Science Advances sets out to answer this question and, after analysing data from 1,270 postmortem brains, the research team identified significant shifts in cell types that may pave the way for improved diagnostic and treatment strategies for patients.
The team used DNA methylation profiles as “fingerprints” for each of seven key cell types, including neurons, microglia (immune cells of the brain), endothelial cells (forming blood vessels) and oligodendrocytes (cells that speed up electrical signals from neurons) with the goal of determining whether changes in these cell types are linked to Alzheimer’s disease, autism, and schizophrenia.
The team found relationships between specific cell changes and neuropsychiatric disorders, including:
Loss of endothelial cells in Alzheimer’s disease
Increased microglia in autism
Reduced oligodendrocytes with schizophrenia.
Interestingly, the team used genetic data to infer that endothelial cells may casually contribute to Alzheimer’s disease, supporting a role for impaired brain vasculature in the disease process. It is unclear whether the autism/microglia and oligodendrocyte/schizophrenia associations reflect cause of consequence.
The study also revealed that age and sex significantly affected the proportions of several cell types, highlighting how neuropsychiatric disorders can be influenced by a combination of genetic risk factors, age, and sex. They also found genetic contributors to brain cell changes.
Dr Yap said that these results improve our understanding of the cellular basis of these neuropsychiatric conditions, and lead to new research avenues.
“Our work adds cellular-level evidence for the relationship between vascular health and Alzheimer’s disease. This prompts us to explore these findings to aid prevention, diagnosis and treatment,” she said.
The full article, titled “Brain cell-type shifts in Alzheimer’s disease, autism, and schizophrenia interrogated using methylomics and genetics” was published in the journal Science Advances in May 2024.
