Project Overview

Childhood stress increases the risk of Alzheimer’s Disease (AD). Early signs of AD appear in a part of the brain that produces serotonin, a chemical important for mood and memory-both of which are affected in AD. Serotonin is also sensitive to childhood trauma. Although there is a connection between early stress, serotonin problems, and the onset of AD, this area has not been studied much because we lacked the right tools and animal models.

We developed an animal model to mimic the early stages of damage seen in AD patients. We propose that childhood stress accelerates the start and progression of AD. By studying how the serotonin system in the brain is affected by the disease and stress, we aim to identify the earliest changes that lead to worsening brain damage over time.

We will use our established mouse model to study how early life stress disrupts serotonin in the brain and speeds up AD-related damage in later life. Using advanced techniques, we can examine disease-related changes in specific brain circuits with cellular-level precision, which is not feasible in humans. This will help us understand how childhood stress impacts AD-related activity and genetic changes in serotonin cells, moving us closer to identifying early biomarkers of the disease.

We identified problems in serotonin cells during the early stages of AD. Our new mouse model mimics early changes in serotonin, and behavioural problems that appear years before dementia. With this project, we will identify the earliest changes in brain connections that put people at increased risk of developing AD. Our goal is to explain why these changes happen, which could help to guide strategies to protect the brain by intervening before the disease worsens.

An early Alzheimer’s diagnosis is an important goal but it is only helpful if effective treatments are available. Existing models, which investigate the standard AD pathological proteins, have resulted in decades of unsuccessful trials.Our new model shifts the focus of intervention to where impairments begin in the brain. This project aims to find out how early risk factors lead to AD, with the goal of helping to develop treatments before disease advances.

Principal Investigator

Derya Sargin , University of Calgary

Partners and Donors

Alzheimer Society of Canada