Understanding Why Women Are Twice as Likely to Develop Alzheimer's Disease

Recent scientific investigations have shed light on the persistent question of why women are twice as susceptible to developing Alzheimer's disease compared to men. This disparity cannot be fully explained by the fact that women tend to live longer, suggesting that biological factors play a significant role.

Research has identified two key contributors to this difference: genetic variations related to chromosomes and hormonal changes associated with menopause. Women possess two X chromosomes, whereas men have one X and one Y chromosome. Genes located on the X chromosome are involved in immune function, brain development, and the pathology of Alzheimer’s disease. The imbalanced gene expression resulting from the presence of two X chromosomes, combined with the incomplete inactivation of one X, may influence disease risk.

Hormonal shifts, particularly during menopause, are another crucial factor. Estrogen and progesterone, hormones prominent in women, have neuroprotective effects. As women reach menopause and estrogen levels decline, their brain's vulnerability to neurodegeneration increases. Studies have demonstrated that hormone replacement therapy (HRT) can impact brain pathology, especially related to tau protein accumulation, which is central to Alzheimer’s progression.

Notably, recent findings indicate that women undergoing HRT later in life show increased tau accumulation and cognitive decline, emphasizing the importance of the timing of hormone therapy. These outcomes support the 'timing hypothesis,' which suggests that HRT may be beneficial if started around menopause but could be harmful if initiated later.

Additionally, sex-related differences are observed in the prevalence of other neurological conditions: multiple sclerosis and migraines are more common in women, while Parkinson’s disease and brain tumors are more prevalent in men. These patterns further underline the biological influence of sex chromosomes and hormones in neurological health.

Understanding these biological differences enhances our knowledge of Alzheimer’s disease and opens new pathways for personalized prevention and treatment strategies. Recognizing the roles of sex chromosomes and hormone levels may be pivotal in developing targeted therapies and developing more effective preventative measures for men and women alike.

Source: https://medicalxpress.com/news/2025-07-women-alzheimer-men.html