The onset of diabetes, hypertension or obesity in middle age constitute some of the biggest risk factors for developing Alzheimer’s at age 65 and older.

New funding from Templeton Research Foundation is supporting NEOMED researcher Christine Dengler-Crish, Ph.D., as she investigates how early damage to a critical vasculature structure called the blood brain barrier (BBB) enables the onset of brain changes that lead to Alzheimer’s disease (AD) and other forms of dementia.

Looking at the Blood Brain Barrier’s Role in Dementia

Diabetes, hypertension and obesity (known as cardiometabolic diseases) damage blood vessels and challenge the body’s ability to transport energy to cells that need it—including the neurons of the brain. The BBB is a highly specialized structure that filters which molecules and substances can move from blood circulation into the brain.

“In AD, there is evidence that the BBB fails to perform these critical functions, allowing neurotoxic pathologies to accumulate in the brain,” explains Dr. Dengler-Crish, an assistant professor in the Department of Pharmaceutical Sciences and adjunct faculty in the Department of Anatomy and Neurobiology. Her work in pre-degenerative pathologies is part of the Neurodegenerative Disease and Aging Research Focus Area at NEOMED.

In this funded pilot project, titled “Identifying new molecular mechanisms for preventing : Integrin proteins and the blood brain barrier,” Dr. Dengler-Crish’s team will determine whether dysfunctional cell-surface proteins called integrins cause early damage to the BBB in transgenic AD-model mice, leaving their brains vulnerable to AD pathology.

“We will test whether we can protect the BBB by administering agents known to modulate integrin signaling and assess their impact on BBB structural proteins and the emergence of brain pathology in AD mice,” explains Dr. Dengler-Crish.

By completing this study, Dr. Dengler-Crish will develop supporting data for a large-scale federal grant application that she plans to submit. And, she adds, “It will further our overall research objective: to find ways to prevent the neurodegenerative process of AD from ever starting.”