The TMEM106B T186S coding variant increases neurite arborization and synaptic density in primary hippocampal neurons.

ABSTRACT: The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer's disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with resilience. Only one coding polymorphism distinguishes the two alleles, a threonine-to-serine substitution at residue 185 (186 in mouse), that is inherited in disequilibrium with multiple non-coding variants. Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in human subjects with the protective haplotype, while murine in vitro studies reveal dramatic effects of TMEM106B deletion on neuronal development. Despite this foundation, the field has not yet resolved whether coding variant is biologically meaning

SUBMITTER: Nguyen Q 

PROVIDER: S-EPMC10603297 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature