Alzheimer's disease is more common in girls than boys? New study reveals key factors

Compiled by: Gong Zixin

Alzheimer's disease is nearly twice as common in women as in men, but the biological mechanisms underlying this difference are unclear. Although beta-amyloid (Aβ) burden levels are similar in both sexes, research suggests that women may be more susceptible to tau pathology, a protein that is closely associated with neurodegeneration and cognitive decline.

Recently, an international research team led by Massachusetts General Hospital and Harvard Medical School conducted a meta-analysis showing that women with higher Aβ levels accumulate tau protein in key brain regions significantly faster than men. The findings suggest that sex differences in Alzheimer's disease pathology may affect treatment outcomes, so it is necessary to develop sex-specific treatment strategies.

The paper was published March 3 in the journal JAMA Neurology.

In this study, the researchers conducted a meta-analysis of longitudinal data from six major aging and Alzheimer's disease studies, including the Alzheimer's Disease Neuroimaging Project, the Berkeley Aging Cohort Study, the Harvard Aging Brain Study, etc. The longitudinal data were collected between November 2004 and May 2022.

The main analysis focused on mixed-effects models to evaluate the relationship between sex, Aβ status, and tau accumulation during a mean follow-up of 2.8 years and to examine whether sex modifies the relationship between apolipoprotein Eε4 (APOEε4) carrier status and tau accumulation.

The study involved 1,376 participants without cognitive impairment, with a mean follow-up of 2.8 years and a mean age of 71.9 years, of whom 55% were women. At baseline, 401 participants (29%) showed high Aβ levels and 412 participants (30%) carried the APOE ε4 allele. Longitudinal tau protein accumulation was measured using positron emission tomography.

The results showed that among individuals with higher Aβ levels, women accumulated tau protein significantly faster than men in specific brain regions (inferior temporal cortex, temporal fusiform gyrus, and lateral occipital cortex).

In addition, women carrying the APOE ε4 allele also accumulated tau protein faster in the inferior temporal region. No significant differences were observed in other brain regions. The results suggest that gender differences in the rate of tau protein accumulation may be one of the reasons for the higher incidence of Alzheimer's disease in women.

Elevated tau levels in women with high Aβ levels may accelerate disease progression, necessitating consideration of sex-specificity in future therapeutic interventions. Further research is needed to explore the underlying biological mechanisms, including the role of hormones and genetic factors in sex-specific Alzheimer's disease pathology.

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