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Sex Differences in Neurodegeneration: The Role of the Immune System in Humans

  • Chloe Lopez-Lee
    Affiliations
    Neuroscience Graduate Program, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York

    Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York
    Search for articles by this author
  • Lay Kodama
    Correspondence
    Address correspondence to Lay Kodama, Ph.D.
    Affiliations
    Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York

    Medical Scientist Training Program and Neuroscience Graduate Program, University of California San Francisco, San Francisco, California
    Search for articles by this author
  • Li Gan
    Correspondence
    Li Gan, Ph.D.
    Affiliations
    Neuroscience Graduate Program, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York

    Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York
    Search for articles by this author

      Abstract

      Growing evidence supports significant involvement of immune dysfunction in the etiology of neurodegenerative diseases, several of which also display prominent sex differences across prevalence, pathology, and symptomology. In this review, we summarize evidence from human studies of established and recent findings of sex differences in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis and discuss how sex-specific central nervous system innate immune activity could contribute to downstream sex differences in these diseases. We examine human genomic and transcriptomics studies in each neurodegenerative disease through the lens of sex differences in the neuroimmune system and highlight the importance of stratifying sex in clinical and translational research studies. Finally, we discuss the limitations of the existing studies and outline recommendations for further advancing sex-based analyses to uncover novel disease mechanisms that could ultimately help treat both sexes.

      Keywords

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