WAM spoke to University of Irvine’s Dr. Elizabeth Head about her latest research into the link between Alzheimer’s and Down Syndrome. Learn more about her study funded through the UCI MIND WAM Initiative.


Read the Q&A with Dr. Elizabeth Head below.


WAM: Why are we studying Alzheimer’s disease in people with Down syndrome? Is there a link?

Dr. Head: Within the Down syndrome population, 95% of people have a full extra copy of chromosome 21. This chromosome contains a gene that is responsible for making the beta-amyloid protein that clumps together to form amyloid plaques in the brain, which is a hallmark of Alzheimer’s disease.  Thus, there is a genetic component linking Down syndrome and Alzheimer’s disease. This means that for people with Down syndrome, who make too much of this protein their entire lives, almost all will develop Alzheimer’s disease pathological changes in their brains after 40 years of age. Alzheimer’s disease is the leading cause of death for a person with Down syndrome. However, although people with Down syndrome may have Alzheimer’s disease changes in their brains (not only include plaques but also tangles), changes in learning and memory, signaling dementia, may not happen until over 10-15 years later.   It is also exciting to note that there is a subset of people with Down syndrome who do not develop dementia even in their 60’s, despite having the necessary changes in their brain. Why some people are resilient is one of the big questions we hope to answer one day.


WAM: Are there other factors that contribute to people with Down syndrome being at higher risk for Alzheimer’s?

Dr. Head: Absolutely. People with Down syndrome have a higher frequency of sleep apnea (ie. have poor sleep), being overweight, and obesity and hypothyroidism that can contribute to a higher risk of Alzheimer’s disease, independently of genetic causes.  Interestingly, hypertension and atherosclerosis are far less frequent, suggesting that people with Down syndrome may be protected from some of the vascular risk factors that typically drive a higher risk of dementia in the general population.


WAM: We are funding a study you are conducting into the role of estrogen receptors and the risk for developing Alzheimer’s. What are you looking for and what do you hope to discover?

Dr. Head: We think that estrogen and its receptors in the brain may be lower in women with Down syndrome after menopause and with advanced age and leads to the brain being more vulnerable to the consequences of amyloid plaques and tangles. Estrogen activates a cascade of protective events in the brain. By understanding the protein pathways that change as estrogen declines, we may find new targets for future interventions for people with Down syndrome and by extension to all women.


WAM: You say women with Down syndrome go through menopause earlier. Do we know why—and what the consequences might be in their risk for developing Alzheimer’s?

Dr. Head: Unfortunately, menopause in women with Down syndrome is vastly understudied. This is yet another reason why we’re hoping to add this body of research, but also inspire others to look into this as well. As for why, the leading theory is that it could be related to thyroid disorders which commonly co-occur with Down syndrome.

In the general population, women do have a higher incidence of Alzheimer’s and are believed to be at higher risk. There is evidence suggesting that this is also true for women with Down syndrome, though if this is related to the onset of menopause is still under investigation. If menopause does increase the risk of Alzheimer’s disease due to a dramatic drop in estrogen, this could increase the rate and severity at which cognitive deficits develop.


WAM: Given estrogen acts as a neural protector and menopause is the primary reason estrogen declines in women, would you advise most women with  Down syndrome to take hormone replacement therapy and why?

Dr. Head: This is an excellent question and also up for debate in the field. It is also important to distinguish that when talking about hormone replacement therapy (HRT) in this context, we are referring specifically to estrogen replacement therapy (ERT) exclusively and not other therapies. Another important thing to consider is the timing of ERT administration. There’s a growing body of research to support that ERT prior to the onset of dementia correlates with better performance on cognitive exams, while ERT after onset can lead to no change or even adverse effects. In short, it is an important conversation to start having with physicians and caregivers to consider potential benefits and side effects.