We recently reported increased mitochondrial fission and decreased fusion, 
increased amyloid beta (Aβ) interaction with the mitochondrial fission protein 
Drp1, increased mitochondrial fragmentation, impaired axonal transport of 
mitochondria and synaptic degeneration in neurons affected by AD. In the present 
study, we extended our previous investigations to determine whether 
phosphorylated tau interacts with Drp1 and to elucidate mitochondrial damage in 
the progression of AD. We also investigated GTPase activity, which is critical 
for mitochondrial fragmentation, in postmortem brain tissues from patients with 
AD and brain tissues from APP, APP/PS1 and 3XTg.AD mice. Using 
co-immunoprecipitation and immunofluorescence analyses, for the first time, we 
demonstrated the physical interaction between phosphorylated tau and Drp1. 
Mitochondrial fission-linked GTPase activity was significantly elevated in the 
postmortem frontal cortex tissues from AD patients and cortical tissues from 
APP, APP/PS1 and 3XTg.AD mice. On the basis of these findings, we conclude that 
Drp1 interacts with Aβ and phosphorylated tau, likely leading to excessive 
mitochondrial fragmentation, and mitochondrial and synaptic deficiencies, 
ultimately possibly leading to neuronal damage and cognitive decline. Treatment 
designed to reduce the expression of Drp1, Aβ and/or phosphorylated tau may 
decrease the interaction between Drp1 and phosphorylated tau and the interaction 
between Drp1 and Aβ, conferring protection to neurons from toxic insults of 
excessive Drp1, Aβ and/or phosphorylated tau.