Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.

ABSTRACT: Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) play crucial roles in neuronal development, synaptic transmission, and neuroplasticity. Deficits in BDNF/TrkB signalling and trafficking have been identified in several neurodegenerative diseases, including Alzheimer's disease (AD). Individuals with Down syndrome (DS) are at an increased risk of developing AD compared to the general population. Basal forebrain neurons (BFNs) are among the first to degenerate in AD and DS, but the mechanisms underlying their vulnerability remain unclear. Using BFNs derived from the Dp1Tyb mouse model of DS, we investigated neurotrophic signalling and trafficking deficits in AD-DS. We found enlarged early endosomes and elevated levels of active Rab5, a GTPase critic

SUBMITTER: Blackburn E 

PROVIDER: S-EPMC12921309 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature