Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.

Presynaptic accumulation of APP-CTFβ increases synaptic activity and may drive early synaptic dysfunction in Alzheimer's disease.

• Why it matters: Understanding early synaptic changes is crucial because they precede cognitive decline, and targeting these processes could offer new therapeutic strategies for AD.
• What they did: The researchers examined endogenous APP and APP-CTFs at excitatory synapses, using pharmacological modulation, post-mortem brain analysis, and Aβ preparations to assess their effects on synaptic transmission and network activity.
• The result: They found that APP-CTFβ accumulation promotes vesicle docking defects and hyperexcitability, with elevated levels in AD brains, and that Aβ can counteract this hyperactivity, highlighting a potential early pathogenic mechanism.