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Table 1 Summary of potential targets of antidepressant drugs in relate to AD pathology

From: Antidepressants are a rational complementary therapy for the treatment of Alzheimer's disease

Antidepressants Neurogenesis Learning & memory NMDA Receptors
Increase synaptic density in hippocampus[75] Does not interact with Aβ fibrils [159]. Protects hippocampal LTP [100]. Performance improvement in Morris water maze after chronic treatment [102]. Inhibit NMDA receptor directly [127].
Does not increase synapse number but reduce decline in synaptic density [76].   Blocks age --induced deterioration of learning and memory [105].  
Prevents the reduction of dendrites length as a result of chronic stress [77].   Protects hippocampal LTP [99, 100]. No effects on animal performance in Morris water maze[102] but improve animal performance is radial maze discrimination task [104].  
TCA    Reduce LTP in CA1 pyramidal cells [96, 97]. Inhibit NMDA receptor directly [124, 125].
   Performance improvement in Morris water maze after chronic treatment [101, 103].  
  Increase secreted APP, reduces intracellular APP in culture [165]. No effect on animal performance in Morris water maze [101] and even worsen spatial working memory in radial arm maze test [106]. Changes in binding to NMDAR [118, 120]and expression of NMDAR in brain [116]
  Increase the levels of secreted APP in the medium of the treated neurons [165].   Adaptation of NMDAR complex [117]. Changes in expression of NMDAR [116].
Clomipramine (NSRI)     Chronic administration changes the regulation of NMDA receptor control on the release of dopamine [119].
    Antagonize NMDA receptor uncompetitively [126].
  Reduces levels of Aβ and tau in Tg mice and cells [157, 161164]