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

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 r...

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Bibliographic Details
Published in:Biological psychiatry (1969) 2022-01, Vol.91 (1), p.72-80
Main Authors: Lopez-Lee, Chloe, Kodama, Lay, Gan, Li
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Female
GWAS
Humans
Immune responses
Immune System
Inflammation
Male
Neurodegeneration
Neurodegenerative Diseases - genetics
Parkinson Disease
Sex Characteristics
Sex difference
Transcriptomics
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Summary: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.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2021.01.002