2024
Alzheimer’s disease (AD) is a major cause of dementia, especially in older adults, and poses a significant public health challenge in the U.S. and worldwide. Women are more affected by AD than men, making up nearly two–thirds of the over 6 million Americans with the disease. Even when accounting for their longer lifespans, women are still more prone to AD and tend to have higher levels and stronger immune responses. Autoantibodies (AAbs) are a type of antibodies that target the body’s own substances instead of external agents such as bacteria or viruses. Some AAbs help fight infections and clear away dead cells, but others can harm the brain. Studies on animals show that high levels of certain AAbs can appear before AD symptoms, like brain plaques and tangles. A few human studies link AAbs to cognitive decline and AD, but these studies often have limitations, such as small sample sizes and only looking at a few AAbs. Additionally, these studies usually collect blood samples after AD has started, and therefore, the levels of AAbs can be influenced by the presence of disease or treatments. Since AD development often begins long before symptoms appear, often in midlife, it is important to find early biomarkers to identify those at risk. However, no studies have looked at the connection between AAbs in midlife and the risk of developing AD at an older age. Using cutting-edge machine learning methods, we will conduct the first study to discover midlife AAbs linked to AD risk and to develop a predictive model that integrates these AAbs with other midlife risk factors. We will leverage the resources from the New York University Women’s Health Study (NYUWHS), a long-term study of over 14,000 women who gave blood samples between 1985 and 1991 when they were 35-65 years old. We will use a comprehensive microarray covering over 21,000 AAbs to measure AAbs in serum samples from 120 women with AD and 120 without. This study will discover new blood biomarkers for AD, which could improve risk assessment in women and potentially lead to new treatments.