Against all odds: Uncovering the mechanisms underlying neurocognitive resilience in individuals with Alzheimer´s pathology
Description: Alzheimer’s disease (AD) is defined by amyloid and tau buildup in the brain. While these proteins are hallmarks of AD, some older adults exhibit high amyloid and tau but stay cognitively healthy (CH) throughout life. This contradiction is supported by post-mortem work, the gold standard for AD diagnosis, which raises crucial questions about the core mechanisms of cognitive health in the presence of brain pathology. Yet research focuses on predicting AD and its progression. Understanding why some people never develop AD is largely unexplored. The project aims to identify and characterize mechanisms underlying neurocognitive resilience in individuals with AD pathology. We will examine the distribution of amyloid and tau in people with high load of both proteins but who remain CH and compare them to AD cases. These resilient individuals have similar protein buildup as those with AD, but the spatial distribution may differ. Second, we will compare brain connectivity between the groups. Third, we will predict who, among those with high amyloid and tau, does not develop AD and identify cognitive domains most contributing to this distinction using an advanced multilayer approach. Lastly, we will use a population-based study to characterize cognitive, brain, lifestyle, and inflammation trajectories in relation to AD pathology for up to 30 years. This work can help find alternative pathways driving cognitive decline and identify who benefits from new treatments for amyloid clearance.
Funder: Vetenskapsrådet
Amount: SEK 4,395,000
Funding type: research
Funder scheme: Project grant
Start date: 2026-01-01
End date: 2028-12-31
Investigator: Bárbara Avelar Pereira
Institution: Karolinska Institutet
Funded outputs count: 2
Funder award ID: 2025-00680
OpenAlex ID: G3047096532