PRADA: Protection Against Dementia in Antioquia (Colombia)

Our research team has been working with families in Antioquia, Colombia, where we’ve identified several inherited forms of early-onset dementia caused by rare genetic mutations. One of the largest families we’ve studied includes about 6,000 relatives, with more than 1,200 people carrying a gene mutation known as Presenilin-1 E280A (PSEN1), which leads to early-onset Alzheimer’s disease. We’ve also identified families with other inherited conditions, like CADASIL (caused by mutations in the NOTCH3 gene) and frontotemporal dementia (linked to MAPT gene mutations).

Through a long-standing collaboration with the Universidad de Antioquia, we’ve discovered that some individuals in these families, even though they carry these high-risk mutations, have remained cognitively unimpaired well into old age. These rare cases may be protected by “resistance” genes (which prevent disease from developing in the brain) or “resilience” genes (which allow people to stay cognitively healthy despite having disease in the brain).

To study this further, we launched the Protection Against Dementia in Antioquia (PRADA) project—the first study to investigate how people from families with Alzheimer’s, CADASIL, or frontotemporal dementia might be naturally protected. We’re testing whether certain genetic variants we’ve found in people with Alzheimer’s, like the APOE3 Christchurch (Arboleda-Velasquez et al., 2019) or the Reelin-COLBOS variants (Lopera et al., 2023) could also protect against other types of dementia.

These exceptional individuals offer a rare window into what protects the brain from dementia. By studying them, we hope to unlock new strategies to prevent and treat Alzheimer’s and other neurodegenerative diseases—not just in Colombia, but globally.

Brain Resilience & Healthy Longevity in Latin America

As we age, the risk of memory and thinking problems goes up—but many older adults stay sharp, even when their brains show signs of Alzheimer’s disease. In fact, about one in three elderly people with Alzheimer’s-related changes like amyloid and tau never develop dementia. Some seem to resist these changes, while others stay cognitively healthy despite them.

In collaboration with the Universidad de Antioquia, we launched a study in Colombia to understand this resilience in the oldest-old. Over the past two years, we’ve expanded the effort to include participants from Peru, Chile, and Costa Rica. Our goal is to uncover what protects brain health in aging across diverse Latin American communities.