Home Current Issue Previous Issues Published Ahead-of-Print Collections For Authors Journal Info
Skip Navigation LinksHome > November 2011 - Volume 70 - Issue 11 > Truncation of tau at E391 Promotes Early Pathologic Changes...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e31823557fb
Original Articles

Truncation of tau at E391 Promotes Early Pathologic Changes in Transgenic Mice

McMillan, Pamela J. PhD; Kraemer, Brian C. PhD; Robinson, Linda BSci; Leverenz, James B. MD; Raskind, Murray MD; Schellenberg, Gerard PhD

Supplemental Author Material
Collapse Box

Abstract

Proteolytic cleavage of tau at glutamic acid 391 (E391) is linked to the pathogenesis of Alzheimer disease (AD). This C-terminal-truncated tau species exists in neurofibrillary tangles and abnormal neurites in the brains of AD patients and may potentiate tau polymerization. We generated a mouse model that expresses human tau truncated at E391 to begin to elucidate the role of this C-terminal-truncated tau species in the development of tau pathology. Our results show that truncated but otherwise wild-type human tau is sufficient to drive pretangle pathologic changes in tau, including accumulation of insoluble tau, somatodendritic redistribution, formation of pathologic conformations, and dual phosphorylation of tau at sites associated with AD pathology. In addition, these mice exhibit atypical neuritic tau immunoreactivity, including abnormal neuritic processes and dystrophic neurites. These results suggest that changes in tau proteolysis can initiate tauopathy.

© 2011 American Association of Neuropathologists, Inc

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.