Women with Down syndrome may develop Alzheimer’s disease more rapidly than men

Women with Down syndrome have more advanced signs of Alzheimer’s disease than men do at the average age of diagnosis, which is the same for both sexes, according to research by the University of California, Irvine. The findings, published in Alzheimer’s & Dementia, can shape how we understand and approach treatments for Alzheimer’s in this population and beyond.

“If women with Down syndrome are further along in disease progression at the time of diagnosis, it could change how we time interventions and interpret outcomes in clinical trials,” said corresponding author Elizabeth Head, UC Irvine professor of pathology. “This research could help tailor therapies more effectively, not just for people with Down syndrome, but for the broader Alzheimer’s population as well.”

Alzheimer’s disease is the primary cause of death for individuals with Down syndrome, who are genetically predisposed to develop the condition earlier in life. While previous studies observed that women with Down syndrome may live longer with dementia than men who have Down syndrome, few have looked closely at whether the underlying brain pathology differs by sex.

In this study, the researchers examined postmortem brain samples from the UC Irvine Alzheimer’s Disease Research Center Brain Tissue Repository and the NIH NeuroBioBank, measuring levels of two hallmark Alzheimer’s proteins: beta amyloid and phosphorylated tau.

The results suggest that women with Down syndrome may carry a higher burden of these disease-related proteins than men, particularly in the occipital lobe, which is an area typically affected later in disease both for people with Down syndrome and for women with sporadic Alzheimer disease—the more common, late-onset form of Alzheimer’s that occurs without a clear genetic cause.

This insight points to the need for more sex-specific approaches in both Alzheimer’s research and treatment planning, especially in the design of clinical trials.

“Understanding selective vulnerabilities within the brain and how these differ in women versus men will help us to better navigate treatment outcomes. We’re learning the importance of modifiable risk factors, which includes accounting for sex-specific risk,” said the study’s lead author, Elizabeth Andrews, a Ph.D. candidate in Head’s lab group.

The research team will next investigate whether sex-based differences extend to other types of pathology—such as blood vessel integrity, white matter connectivity and additional contributors to dementia—and how those findings correlate with biomarker data collected during life. These efforts will help advance the field of precision medicine and offer more personalized strategies for Alzheimer’s care and prevention.

Women with Down syndrome have more advanced signs of Alzheimer’s disease than men do at the average age of diagnosis, which is the same for both sexes, according to research by the University of California, Irvine. The findings, published in Alzheimer’s & Dementia, can shape how we understand and approach treatments for Alzheimer’s in this population and beyond.

“If women with Down syndrome are further along in disease progression at the time of diagnosis, it could change how we time interventions and interpret outcomes in clinical trials,” said corresponding author Elizabeth Head, UC Irvine professor of pathology. “This research could help tailor therapies more effectively, not just for people with Down syndrome, but for the broader Alzheimer’s population as well.”

Alzheimer’s disease is the primary cause of death for individuals with Down syndrome, who are genetically predisposed to develop the condition earlier in life. While previous studies observed that women with Down syndrome may live longer with dementia than men who have Down syndrome, few have looked closely at whether the underlying brain pathology differs by sex.

In this study, the researchers examined postmortem brain samples from the UC Irvine Alzheimer’s Disease Research Center Brain Tissue Repository and the NIH NeuroBioBank, measuring levels of two hallmark Alzheimer’s proteins: beta amyloid and phosphorylated tau.

The results suggest that women with Down syndrome may carry a higher burden of these disease-related proteins than men, particularly in the occipital lobe, which is an area typically affected later in disease both for people with Down syndrome and for women with sporadic Alzheimer disease—the more common, late-onset form of Alzheimer’s that occurs without a clear genetic cause.

This insight points to the need for more sex-specific approaches in both Alzheimer’s research and treatment planning, especially in the design of clinical trials.

“Understanding selective vulnerabilities within the brain and how these differ in women versus men will help us to better navigate treatment outcomes. We’re learning the importance of modifiable risk factors, which includes accounting for sex-specific risk,” said the study’s lead author, Elizabeth Andrews, a Ph.D. candidate in Head’s lab group.

The research team will next investigate whether sex-based differences extend to other types of pathology—such as blood vessel integrity, white matter connectivity and additional contributors to dementia—and how those findings correlate with biomarker data collected during life. These efforts will help advance the field of precision medicine and offer more personalized strategies for Alzheimer’s care and prevention.