REELIN-COLBOS (H3447R) in Colombian oldest-old individuals, a case series

We previously identified <i>REELIN-</i>COLBOS (<i>RELN</i> H3447R) and <i>APOE</i> Christchurch (<i>APOE</i> R136S) as candidate gene variants associated with protection against dementia in cases at the highest risk of Alzheimer's Disease (AD) due to the <i>PSEN1</i> 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 <i>REELIN</i>-COLBOS variant were identified and described here, whereas none of the cases carried <i>APOE</i> 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.