Brain Canada Brain Canada
FR Donate

Serotonin circuit dysregulation in Alzheimer’s Disease

Principal Investigator:
  • Derya Sargin, University of Calgary
  • Alzheimer's Association

Project Overview

Alzheimer’s Association International Research Grant Program: Alzheimer’s Association Research Grant (AARG)

Today, more than six million people in North America are living with dementia, with an estimated annual economic burden of $150 billion for patients and caregivers. Alzheimer’s Disease (AD) is the most common form of dementia that results in severe loss of brain cells and cognitive decline. Memory problems are the most recognized symptoms of AD. However, behavioral symptoms including mood changes and social impairment are observed years before memory deficits. The early detection of these symptoms is critical for disease intervention. Serotonin is a chemical produced by brain cells that are central to mood, social and cognitive regulation. Serotonin cells are among the earliest cells that are destroyed in the brain of AD patients. They reside in a brain region that is now classified as one of the first to show AD pathology. The disruption of the serotonin system early in disease is thought to underlie the emergence of behavioral symptoms in AD. Yet, how this happens is unknown. A strong risk factor for AD is stress experienced early in life. My lab discovered that early life stress in an animal model disrupts the serotonin system leading to behavioral symptoms reminiscent of those observed in AD. This work will investigate how serotonin dysfunction early in disease progression disrupts brain function in AD, with early life stress as an environmental risk factor. We will use this knowledge to manipulate serotonin activity to reverse the chronicity of AD-related symptoms.