Abnormal interaction of oligomeric amyloid-β with phosphorylated tau: implications to synaptic dysfunction and neuronal damage.

Alzheimer's disease (AD) is a progressive neurodegenerative mental illness characterized by memory loss, multiple cognitive impairments, and changes in personality and behavior. The purpose of our study was to determine the interaction between monomeric and oligomeric amyloid-β (Aβ) and phosphorylated tau in AD neurons. Using postmortem brains from AD patients at different stages of disease progression and control subjects, and also from AβPP, AβPPxPS1, and 3xTg-AD mice, we studied the physical interaction between Aβ and phosphorylated tau. Using immunohistological and double-immunofluorescence analyses, we also studied the localization of monomeric and oligomeric Aβ with phosphorylated tau. We found monomeric and oligomeric Aβ interacted with phosphorylated tau in neurons affected by AD. Further, these interactions progressively increased with the disease process. These findings led us to conclude that Aβ interacts with phosphorylated tau and may damage neuronal structure and function, particularly synapses, leading to cognitive decline in AD patients. Our findings suggest that binding sites between Aβ and phosphorylated tau need to be identified and molecules developed to inhibit this interaction.