Alex R. DeCasien, Ph.D.

Dr. DeCasien is an evolutionary neuroscientist and computational biologist at the National Institute on Aging whose research focuses on the genetic, hormonal, molecular, and evolutionary basis of sex differences in brain aging and neurodegenerative disease. Their group integrates single-cell genomics, transcriptomics, epigenomics, endocrinology, and comparative biology to understand how sex-related mechanisms shape variation in brain health across individuals and throughout the lifespan.

Across neurodegenerative diseases, sex differences are observed in prevalence, clinical presentation, progression, and outcomes. Yet the biological origins of these differences–and how they interact with aging–remain poorly understood. Dr. DeCasiens research addresses this gap by investigating how the sex chromosomes, hormones, and other sex-related processes influence resilience and vulnerability to neurodegeneration. This work seeks to reveal fundamental mechanisms of disease, identify opportunities for prevention, and advance more precise approaches to diagnosis and treatment.

A major focus of the DeCasien group is defining the role of the sex chromosomes in the aging human brain. The group is developing improved methods for quantifying X- and Y-chromosome expression in single-cell RNA sequencing data and identifying the evolutionary and regulatory mechanisms that drive sex-biased gene expression. Their work also examines how age-related erosion of X-chromosome inactivation and mosaic loss of the Y chromosome alter the molecular landscape of the brain and potentially contribute to neurodegenerative disease.

Dr. DeCasien also leads CHARMSS, a collaboration spanning multiple NIH Institutes and Centers that integrates peripheral hormone measurements with brain transcriptomic data to uncover the hormonal drivers of sex differences in brain aging. By connecting systemic endocrine changes with molecular processes in the brain, CHARMSS aims to clarify how hormonal trajectories across the lifespan shape brain health and disease risk.

The DeCasien group also places its human findings within a broader evolutionary and organism-wide framework. The group is developing a cross-tissue, multi-omic atlas of aging and sex effects in rhesus macaques, enabling the identification of conserved and human-specific mechanisms across tissues, cell types, and stages of the lifespan.

Dr. DeCasiens earlier work demonstrated functional differences between genes shared by the X and Y chromosomes, characterized sex differences in the human brain transcriptome at cell-type resolution, and established conceptual and methodological recommendations for research on sex differences in the brain. They received the Organization for the Study of Sex Differences 2024 Early Career Award in recognition of these contributions.

Dr. DeCasien received their B.S., M.A., M.Phil., and Ph.D. from New York University. They completed their postdoctoral training in the Section on Developmental Neurogenomics at the National Institute of Mental Health, where they studied the genomic and evolutionary foundations of sex differences in the human brain. Dr. DeCasien now leads an independent research group within the Laboratory of Neurogenetics at the National Institute on Aging.