Summary
A bioRxiv preprint reports that deleting truncated TrkB receptors in astrocytes reduced amyloid plaques and preserved synaptic markers in 5xFAD mice. The findings are from a mouse model, not a human treatment study.
A bioRxiv preprint posted on October 24, 2026, reports that removing truncated TrkB receptors from astrocytes reduced amyloid plaques and protected synaptic markers in 5xFAD mice, a model of Alzheimer’s disease. The researchers used an astrocyte-specific genetic deletion, so the results identify a possible disease mechanism in mice rather than demonstrating a treatment effect in people.
Why the researchers targeted truncated TrkB
Brain-derived neurotrophic factor (BDNF) supports nervous-system function, acting mainly through the full-length TrkB receptor, called TrkB.FL. The Ntrk2 gene also produces truncated forms, TrkB.T1 and TrkB.T2, which lack the receptor’s intracellular tyrosine kinase domain. These truncated forms are found predominantly in astrocytes, support cells in the brain. They are thought to dampen BDNF–TrkB.FL signalling by binding BDNF or forming signalling-deficient complexes with the full-length receptor.
To test whether reducing this influence could affect Alzheimer’s-like pathology, the team deleted Ntrk2 in astrocytes when the mice were five weeks old. Cortical TrkB.T expression fell by more than 80%, while TrkB.FL levels were unchanged. The researchers also found larger Bassoon-positive presynaptic active zones, a result consistent with increased BDNF–TrkB.FL signalling.
Plaques and synaptic markers in the mice
In six-month-old 5xFAD mice, the deletion reduced β-amyloid plaque burden by more than 60% in the cortex, hippocampus and subiculum. The researchers reported no detectable change in microgliosis or astrogliosis, measures of increased activity or presence of these brain immune and support cells.
At one year of age, the mice with astrocytic TrkB.T ablation were protected from reductions in both the density and size of PSD-95-positive postsynaptic sites in the cortex and hippocampus. PSD-95 marks structures at the receiving side of synapses; the finding therefore points to preservation of a specific synaptic measure, rather than a direct count of every synapse in the brain.
Together, the results link astrocytic TrkB.T to amyloid pathology and synaptic changes in this mouse model. Selectively reducing the truncated receptors could be a way to enhance the brain’s own BDNF signalling, as the authors propose. The work is a preprint, and the findings come from a genetic intervention in 5xFAD mice; they provide a basis for further research, not evidence that this approach benefits people with Alzheimer’s disease.