KRIBB researchers link primate-specific DNA changes to dementia

Researchers at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) have identified a primate-specific genetic mechanism that may contribute to dementia-related neurodegeneration. Using human stem cell-derived brain organoids, the team investigated how Alu elements—short DNA sequences unique to primates—can cause genetic deletions that traditional mouse models cannot replicate.

The study focused on the SPAST gene, which is linked to hereditary spastic paraplegia. While mutations in this gene typically cause motor issues, some patients also experience cognitive decline. The researchers found that a deletion in SPAST exon 17 creates an abnormal connection to the neighboring SLC30A6 gene, resulting in a fusion transcript. This process reduces levels of the zinc transporter ZnT6, leading to abnormal zinc accumulation in the cytoplasm and disrupting intracellular balance, which contributes to neuronal damage.