Clinical Manifestations.

Background: Life expectancy is on the rise, accompanied by an increased prevalence of cognitive impairment and Alzheimer's disease. Despite this global trend, our understanding of the neural mechanisms underlying cognitive changes in the oldest-old (>80 years old) population remains limited. Unraveling these mechanisms may provide valuable insights and therapeutic interventions for individuals grappling with cognitive impairments in older age.

Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

Background: Variants in and (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the variant who also had two copies of the apolipoprotein E3 Christchurch variant ( ). Heterozygosity for the variant may influence the age at which the onset of cognitive impairment occurs.

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.

Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries.

Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances.