Abnormal Interaction of Oligomeric Amyloid-beta with Phosphorylated Tau: Implications to Synaptic Dysfunction and Neuronal Damage

作者：Manczak Maria; Reddy P Hemachandra^*

来源：Journal of Alzheimer's Disease, 2013, 36(2): 285-295.

DOI：10.3233/JAD-130275

• Amyloid-beta
• amyloid-beta protein precursor
• cognitive decline
• phosphorylated tau
• synapses

Alzheimer%26apos;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-beta (A beta) and phosphorylated tau in AD neurons. Using postmortem brains from AD patients at different stages of disease progression and control subjects, and also from A beta PP, A beta PPxPS1, and 3xTg-AD mice, we studied the physical interaction between A beta and phosphorylated tau. Using immunohistological and double-immunofluorescence analyses, we also studied the localization of monomeric and oligomeric A beta with phosphorylated tau. We found monomeric and oligomeric A beta 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 A beta 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 A beta and phosphorylated tau need to be identified and molecules developed to inhibit this interaction.

• 出版日期2013