Microglia mediate Aβ-induced homeostatic synaptic plasticity

Recent studies have highlighted the dual role of amyloid beta peptide (Aβ) in both Alzheimer’s disease (AD) and normal brain function. Particularly, Αβ1-40 and Αβ1-42 are key in regulating homeostatic synaptic plasticity in the dentate gyrus. This study aimed to identify specific amyloid fragments (N- and C- terminus fragments of Αβ) involved in synaptic plasticity modulation. Using entorhino-hippocampal tissue cultures, combined with whole-cell patch clamp recordings, light- and electron microscopy and molecular biology techniques, we found that the N-terminal fragment Aβ1-16 is essential for mediating Aβ-induced homeostatic synaptic plasticity in response to tetrodotoxin (TTX) exposure. Microglia involvement was evident as Αβ1-16 treatment altered microglial morphology and complexity, whereas microglia depletion form the tissue cultures prevented Αβ1-16-induced homeostatic synaptic plasticity. Conversely, the C-terminal fragment, Αβ17-42 did not influence this process. These findings advance our knowledge of the physiological functions of Aβ and its relationship with neurodegeneration, underscoring the critical role of microglia in Aβ-induced synaptic plasticity.