Approved Research

The impact of female reproductive history and APOE genotype on cognitive health

Lay summary

Alzheimer's disease (AD) is characterised by severe memory loss that is accompanied by both a loss of brain cells (including neurons) and disease of brain cells (including plaques and tangles). The lifetime risk of AD is higher in women, irrespective of the fact that women live longer than men. Women with AD also show greater memory loss and brain cell loss than males. One particular gene variant - apolipoprotein E (APOE) isoform !4 - is a well-established risk factor for AD. Interestingly, women who carry this gene variant (APOE!4) show greater risk for AD, brain cell loss, brain levels of plaques and tangles and memory loss in middle age compared to men.

Considering this sex difference, it is important to examine the role that unique female experiences such as pregnancy may play a role in AD. Indeed, pregnancy has long-lasting effects on the brain and in memory which can be associated with a greater risk of dementia including AD. Postmenopausal hormone therapies (HTs) can also affect memory but it is not know how previous pregnancy or the gene variant (APOE!4) influence AD risk in women and we aim to find out how these factors influence risk for AD.

We will use the large database from the UK Biobank to examine how the gene variant (APOE!4) and female-specific factors (HT, previous pregnancy) impact brain aging and AD risk. We expect this project to take approximately 1 year.

This research will provide significant insight on the importance of tailoring treatments based on factors specific to women ( HT, pregnancy) that may explain the greater risk for women to be diagnosed with AD. Our goal is to improve health and treatment of AD for women but our work may also inform on factors related to health in men.