Abstract
We previously identified REELIN-COLBOS (RELN H3447R) and APOE Christchurch (APOE R136S) as candidate gene variants associated with protection against dementia in cases at the highest risk of Alzheimer's Disease (AD) due to the PSEN1 E280A mutation in Colombia. Here, we examined the frequency of these variants in a cohort of 135 Colombian oldest-old individuals, part of the Resist AD Project. Five carriers of the REELIN-COLBOS variant were identified and described here, whereas none of the cases carried APOE Christchurch. The first case is a 102-year-old APOE4/E3 carrier with stable performance on cognitive tests despite having suffered an episode of delirium due to pneumonia. FDG-PET revealed relatively preserved cortical glucose metabolism despite showing degenerative changes on MRI. Another case with a family history of early-onset dementia maintained independence until age 85. Despite significant comorbidities, the other three cases exhibited preserved cognition at baseline. These observations are consistent with the hypothesis that the Reelin-COLBOS variant may play a protective role against cognitive decline and support healthy aging, although further studies are needed in larger and more diverse populations to confirm this association.