2023 Alzheimer's Association Clinician Scientist Fellowship (AACSF)
The Role of Pregnancy History in Women at Risk for Alzheimer’s disease
How may having multiple pregnancies make women more likely to develop Alzheimer’s?
Anna Brugulat-Serrat, Ph.D.
Barcelonabeta Brain Research Center
Barcelona, Spain
Background
According to the 2023 Alzheimer’s Association Facts & Figures report, of the more than 6.5 million Americans aged 65 and older with Alzheimer’s, nearly two-thirds are women. Though the primary reasons for this difference are unknown, research has shown that a woman’s reproductive health, including the number of pregnancies and number of years with menstrual cycles, may affect later-life risk for Alzheimer’s and other dementias. This finding suggests a role in dementia risk for hormones and other contributors to the reproductive pathways. Previous studies with genetically engineered Alzheimer’s-like mice have focused on levels of hormones in later life, but it is unclear how factors related to pregnancy during reproductive age may impact later susceptibility to Alzheimer’s.
In initial studies, Dr. Anna Brugulat-Serrat and colleagues found that cognitively unimpaired women at risk of Alzheimer’s showed higher levels of abnormal tau protein in the cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord) if they had had 3 or more children. Abnormal tau levels in the blood and CSF are key biological markers (biomarkers) of Alzheimer’s. This result suggests that having multiple children may be related to other biomarkers for the disease.
Research Plan
Dr. Anna Brugulat-Serrat and colleagues will now examine medical and cognitive data from around 1,700 cognitively unimpaired women and more than 900 men. The women in the study will have undergone menopause and have had a different number of children. Dr. Brugulat-Serrat’s team will assess the relationship between pregnancy history and (1) levels of dementia-related proteins in the blood and CSF, (2) dementia-related brain inflammation and loss of cell-to-cell communication, and (3) loss of brain blood vessel function. The researchers will also examine how various factors (including genetics, level of education, and socio-economic status) may impact or moderate the role of multiple pregnancies on Alzheimer’s risk.
Impact
Dr. Brugulat-Serrat’s study could improve our understanding of the factors related to brain health and Alzheimer’s in women. It could also lead to novel methods of diagnosing the disease in women and treating it at its early stages.