"The X chromosome represents 5% of the genome in women and men and is understudied in aging and Alzheimer disease. In the brain, more genes are expressed from the X chromosome than from any other single autosome," Dr. Dena B. Dubal of the University of California, San Francisco, and colleagues note in JAMA Neurology.
They examined differential gene expression of the X chromosome in dorsolateral prefrontal cortex obtained at autopsy in 508 elderly individuals (62% women) from the Religious Orders Study and Rush Memory and Aging Project.
At death, the mean age of participants was 88 years, 39% had a clinical diagnosis of AD and 58% had a pathological diagnosis of AD.
After adjusting for age at death, education, and AD pathology, X chromosome gene expression (29 genes) correlated significantly with cognitive change in women but not men. In most of the identified X genes (19 genes), increased expression was associated with slower cognitive decline in women.
In contrast with cognition, the expression of three X chromosome genes, adjusted for age at death and education, was associated with neuropathological tau burden in men but not women.
"A disproportionate density of factors influencing neural function reside on the X chromosome and their roles in aging, AD, and other neurodegenerative diseases require identification and investigation in both sexes," they point out.
"This is important because X factors could contribute understanding of disease-relevant neurobiology along with sex differences and sex specificity of biomarkers, disease courses, and eventually pathways for personalized treatments against pathological aging and AD for women and men," they add.
SOURCE: https://bit.ly/3mFy6eT JAMA Neurology, online August 23, 2021.
By Reuters Staff
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