Women Show Stronger Tau Response to Amyloid and Greater Dementia Risk Impacts

Women exhibit a stronger tau response to amyloid-β than men, with higher plasma phosphorylated tau 217 (p-tau217) levels and greater tau accumulation at biomarker levels, according to a study published in JAMA Neurology. Women are disproportionately affected by Alzheimer disease dementia. Of the seven million adults living with Alzheimer's disease, nearly two-thirds are women.

In this longitudinal multicohort study, researchers analyzed data from 1 clinical trial cohort (A4/LEARN) and 4 observational cohorts, including the Harvard Aging Brain Study (HABS), the Wisconsin Registry for Alzheimer's Prevention (WRAP), the Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) study. The analysis included 1292 adults without cognitive impairment, of whom 63.6% were women and the mean (SD) age was 70.6 (6.4) years. Across cohorts, higher Aβ levels were associated with greater increases in p-tau217 among women compared with men. At comparable p-tau217 levels, women demonstrated greater tau deposition and longitudinal accumulation across several brain regions, including the inferior parietal cortex and entorhinal cortex. In secondary analyses, elevated p-tau217 was associated with faster cognitive decline among women in the WRAP and ADNI cohorts. "These findings add to growing evidence that women have a differential tau response to Aβ that may emerge at the point of p-tau secretion," the authors noted.

Researchers from the University of California San Diego School of Medicine found that women not only experience a higher burden of certain modifiable dementia risk factors, but also appear more vulnerable to their effects on cognitive function. The study, which analyzed data from more than 17,000 middle-aged and older adults, was published on May 19, 2026 in Biology of Sex Differences. Women were more likely than men to report:

• Depression (nearly twice as common in women as men — 17% vs. 9%)
• Physical inactivity (48% vs. 42%)
• Sleep problems (45% vs. 40%)

Men, on the other hand, had:

• Higher rates of hearing loss (64% vs. 50%)
• Diabetes (24% vs. 21%)
• Heavy alcohol use (22% vs. 12%)

Beyond prevalence, the study found that several risk factors were more strongly associated with poorer cognitive performance in women. For example, cardiovascular and metabolic conditions such as hypertension and increased BMI showed steeper negative associations with cognition in women compared to men. However, hearing loss and diabetes — both more common among men — were linked to poorer cognitive scores in women.

Older women in good cognitive health with higher levels of plasma p-tau217 had greater risks for mild cognitive impairment or dementia up to 25 years later, according to a study published by JAMA Network Open. p-tau217 is viewed as a promising biomarker for Alzheimer's disease, allowing clinicians to identify who is susceptible earlier. Women with this biomarker should prioritize consistency in their daily routines, while incorporating any form of physical movement, social engagement, balanced nutrition and activities that keep their brains engaged.

Nearly two-thirds of patients with Alzheimer disease are women, most of them postmenopausal. The estimated lifetime risk for a 45-year-old woman is 1 in 5 — twice that of a man of the same age. Neuroendocrine aging and the hormonal shifts that accompany the menopause transition have emerged as potentially modifiable Alzheimer's disease risk factors in women. By 2050, over 1.2 billion women worldwide will be in or approaching menopause. A review in the Journal of Clinical Investigation calls for a paradigm shift: from viewing Alzheimer's risk as a byproduct of generalized aging to validating midlife neuroendocrine aging as a distinct window of vulnerability, and an opportunity for prevention.