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

Presynaptic accumulation of APP-CTFβ is linked to increased synaptic vesicle docking and network hyperexcitability in Alzheimer's disease.

• Why it matters: Understanding early synaptic changes in AD is crucial because synaptic dysfunction occurs before cognitive decline, and targeting these processes could offer early intervention strategies.
• What they did: The study examined endogenous APP and APP-CTFs at excitatory synapses, used pharmacological modulation, and analyzed post-mortem AD brains to assess APP-CTFβ levels and synaptic alterations.
• The result: Elevated presynaptic APP-CTFβ promotes vesicle docking defects and network hyperexcitability, which can be counteracted by monomeric Aβ, implicating APP-CTFβ in early synaptic dysfunction in AD.