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The number of people diagnosed with neurodegenerative diseases is on the rise. Many of these diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and motor neuron disease, demonstrate clear sexual dimorphisms. While sex as a biological variable must now be included in animal studies, sex is rarely included in in vitro models of human neurodegenerative disease. In this Review, we describe these sex-related differences in neurodegenerative diseases and the blood-brain barrier (BBB), whose dysfunction is linked to neurodegenerative disease development and progression. We explain potential mechanisms by which sex and sex hormones affect BBB integrity. Finally, we summarize current in vitro BBB bioengineered models and highlight their potential to study sex differences in BBB integrity and neurodegenerative disease.

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