Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity

Figure 2

Concentration-dependent effects of Aβ on synaptic function. At normal physiological levels (picomolar range), Aβ peptides have positive effects on synaptic function: they can positively regulate presynaptic release probability and facilitate learning and LTP in CA1 by activating α7-nAChRs. However, when the concentration of Aβ peptides is lower than normal, presynaptic function is impaired. On the other hand, under pathological conditions, such as increased neuronal activity, stress, or the presence of familial Alzheimer’s disease (FAD) mutations, the increase in Aβ peptide concentration produces pathological effects, including decreased presynaptic neurotransmitter release, reduced postsynaptic responsiveness, LTP impairment, and LTD facilitation. Therefore, maintaining the concentration of Aβ peptides within a normal physiological range is essential and should be the goal for developing effective treatments for Alzheimer’s disease.