HCR.20.039 – The role of stress in Alzheimer’s disease.

Route: Health care research, sickness prevention and treatment

Cluster question: 077 What do non-genetic factors contribute to personal traits and disease processes?

The most common cause of dementia is Alzheimer’s disease (AD). People differ in their susceptibility and resilience to the disease process. To date, we do not know the triggers and modifying factors in the pathogenesis that ultimately lead to neuronal loss and cognitive decline. Knowledge of these factors is key to development of a drug that can halt or slow the progression of the disease.
A commonly asked question when talking to patients and care givers is whether stress makes Alzheimer worse. This question is instigated by the high stress levels that patients often experience during the disease process. Stress can be defined as a state that follows an environmental disturbance that exceeds the routine adaptive capacity and resilience of the individual. Although transient stress is an essential survival response, chronic stress is a pathogenic factor that has been implicated in many human diseases including AD. Stress responses as mentioned by patients and caregivers are largely mediated by glucocorticoid hormones. Moreover, chronic psychosocial stress triggers cellular stress responses in the brain, that differ per cell type.
In this project we will address the impact of stress on the incidence and progression of AD by developing and applying a multifactorial stress profile in a longitudinal population-based cohort as well as a clinical AD patient cohort. In parallel, we will combine advanced molecular and cell biological techniques with state-of-the-art bioinformatics and artificial intelligence to identify the molecular pathways involved in stress susceptibility and resilience in AD. The ultimate aim of the project is to determine how stress responses can be modulated to delay the onset or progression of Alzheimer dementia.


Alzheimer's disease, bioformatics, glucocorticoid, neuroinflammation, Stress, tau pathology

Other organisations

Leiden Universitair Medisch Centrum (LUMC), Rijksinstituut voor Volksgezondheid en Milieu (RIVM), Technische Universiteit Delft (TUD)


Organisation Amsterdam UMC (AMC)
Name Dr. W. (Wiep) Scheper
E-mail w.scheper@amsterdamumc.nl
Website https://fga.cncr.nl/research_teams/molecular_neurodegeneration_/