MAPT and Alzheimer disease: In summary, the synaptic attack by ADDLs seems to offer a mechanistic link between various facets of early events in AD pathogenesis such as synapse loss [226], AD-type tau hyperphosphorylation [269], ROS formation [279], brain insulino-resistance [263] and selective neurodegeneration providing strong evidence for their involvement in memory impairment and ultimately dementia [114,115].