2023 Sex and Gender in Alzheimer’s (SAGA) Grant (SAGA)
Using epigenomics to identify Alzheimer’s disease risk in gender dysphoria
Does gender-affirming hormone therapy lead to changes in DNA that could increase risk of Alzheimer’s?
Ivan Nalvarte, Ph.D.
Karolinska Institutet
Solna, Sweden
Background
A transgender person is someone whose gender identity does not correspond with the sex registered for them at birth—they may consider themselves masculine, feminine or nonbinary. Some transgender people receive gender-affirming hormone therapy (GAHT) to reach their goals of gender embodiment and/or to reduce gender dysphoria, which are negative feelings associated with a branching between gender identity and assigned sex. Typically, feminine embodiment GAHT includes estrogen and androgen-lowering medications, and masculine embodiment GAHT includes testosterone.
Little is known about whether GAHT impacts the risk of developing Alzheimer’s. However, some studies have shown disproportionate rates of dementia among transgender relative to cisgender people, those who identify with the sex registered from them at birth.
One way that GAHT might lead to changes in the brain is through epigenetic modification, or the chemical modification of genetic material (DNA). The epigenome is a record of modifications to the DNA that can turn genes “on” or “off” in response to their environment. These DNA modifications could lead to brain cell death and subsequent cognitive impairment.
Research Plan
Dr. Nalvarte will mimic GAHT in genetically engineered Alzheimer’s-like mice and analyze epigenetic changes compared to mice not receiving GAHT. They will compare the data they collect from mice to epigenetic data from individuals in the Swedish Gender Dysphoria cohort, a group of 382 individuals, almost all of whom are receiving GAHT. They aim to identify an epigenetic signature that can predict Alzheimer’s risk. They also aim to determine whether GAHT alters the course, symptoms, or brain changes in Alzheimer’s-like mice.
Impact
The results of this study may help identify epigenetic changes that occur with gender-affirming hormone therapy and understand whether those changes modify risk for Alzheimer’s.