Poccessing five transgenic mutation, 5XFAD have drastically different gene expression (1300 differentially expressed gene at 4 months) compared to wild type. Three mutation are on APP and two mutations are on PS1, together they grant 5XFAD huge production rate of Aβ42, which is a highly amyloidogenic and thus can lead to severe amyloid pathology in various regions in CNS, ranging from subiculum to cortical layer V, from hippocampus to thalamus, etc. 

   Amyloid pathology in 5XFAD is associated with astrogliosis and microgliosis, and the later is in turn linked with microvascular damage, which is another angiopathy linked with amyloidosis beside the progressive cerebral amyloid angiopathy (CAA).

   Worse still, amyloidosis in 5XFAD is also linked with neurites dystrophy, ranging from axonal abnormality to progressive myelin abnormalities, which might be the underlying cause for the synaptic dysfunction in 5XFAD, ranging from decrement in excitability to even synapse loss.

   The synaptic dysfunction might in turn be the reason for the neurodegeneration, especially in cortical layer V, which experience up to about 40% neuronal loss.

   Reasonably, the severe neurodegeneration in 5XFAD might be the cause of its cognitive dysfunction, including progressive working memory deficits and decrement in anxiety, and behavioral dysfunction, including sensorimotor impairments and aberrant reflexes.

   Tauopathy, on the other hand, is not known in 5XFAD.

   Therefore, all in all, 5XFAD might be a great AD model to isolate its amyloid pathology out, amplify and then investigate into its effects within a short time span