Estrogen therapy may fight early Alzheimer's Women who carry a gene that puts them at increased risk for developing Alzheimer's disease show signs of early aging at the cellular level long before the first hints of dementia might set in, when they appear otherwise healthy and active, a team of UCSF and Stanford scientists found. But there's good news, too. When those women used hormone replacement therapy to treat symptoms of menopause, evidence of advanced aging disappeared. After just two years on hormones, women with the gene looked, under a microscope, the same age as their peers without the gene. The research, which was published last week, is still preliminary and only involved a small sample of women with and without the Alzheimer's risk gene. It raises a host of fascinating questions: What effect does the Alzheimer's gene have on aging overall? What role do hormones play in aging? Can replacing the hormones women lose as they age prevent diseases like dementia?There are not many answers, but the research findings add to the already complex and controversial discussion about hormone replacement therapy and who will benefit from it."It appears that women who are at genetic risk for Alzheimer's disease may have more rapid aging, so that's one pretty provocative finding from this study," said Dr. Natalie Rasgon, director of the Stanford Center for Neuroscience in Women's Health and an author of the study paper." The second finding is that it is possible that we're narrowing in on the group of women who benefit the most from hormone therapy," she said. "We're discovering a new direction for research in understanding who may actually benefit from hormones in middle age."
A key variant gene The research focused on a gene called apolipoprotein E, or ApoE, which is responsible for protecting and repairing neurons. There are several types of the ApoE gene, and people who carry the variant known as ApoE4 are four to 14 times more likely to develop Alzheimer's than people without the variant. Recent studies have shown that women with the variant are at more risk for Alzheimer's than men who have it.The UCSF and Stanford study looked at 63 women in their 50s and 60s, a third of whom were carriers of the ApoE4 gene. To study the aging process in these women at the cellular level, they measured the length of participants' telomeres - the protective caps found at the end of every chromosome. Telomeres repeatedly have been shown to become shorter as people age. All of the women in the study had already been on hormone therapy for at least a year when they joined it. When the study started, half of the women were randomly taken off of hormones, and half were instructed to keep taking hormones for two years. Their telomeres were measured both at the start of the two years and at the end. Over that time, women with the ApoE4 gene who were taken off of hormone therapy showed a significant decline in telomere length - a shortening that aged them by seven to 14 years. But women with the gene variant who stayed on the hormone therapy maintained their telomere length.For women who were not carriers of the ApoE4 gene, there was not a noticeable difference in telomere length with or without hormone therapy.
No outward signs Part of what makes the study results so striking, Rasgon said, is that the effects of early aging were found in women, some only in their early 50s, who appeared very healthy and had no outward indication of illness or cognitive decline.These women were no more likely than their peers without the gene variant to have gray hair or wrinkles, or to look or behave older in any way, but their cells appeared a decade older than they should, which could put them at greater risk for developing a whole host of age-related conditions like heart disease, stroke and, of course, Alzheimer's.