TY - JOUR T1 - Blocking Aβ<sub>42</sub> Accumulation Delays the Onset and Progression of Tau Pathology via the C Terminus of Heat Shock Protein70-Interacting Protein: A Mechanistic Link between Aβ and Tau Pathology JF - The Journal of Neuroscience JO - J. Neurosci. SP - 12163 LP - 12175 DO - 10.1523/JNEUROSCI.2464-08.2008 VL - 28 IS - 47 AU - Salvatore Oddo AU - Antonella Caccamo AU - Bert Tseng AU - David Cheng AU - Vitaly Vasilevko AU - David H. Cribbs AU - Frank M. LaFerla Y1 - 2008/11/19 UR - http://www.jneurosci.org/content/28/47/12163.abstract N2 - The molecular alterations that induce tau pathology in Alzheimer disease (AD) are not known, particularly whether this is an amyloid-β (Aβ)-dependent or -independent event. We addressed this issue in the 3xTg-AD mice using both genetic and immunological approaches and show that a selective decrease in Aβ42 markedly delays the progression of tau pathology. The mechanism underlying this effect involves alterations in the levels of C terminus of heat shock protein70-interacting protein (CHIP) as we show that Aβ accumulation decreases CHIP expression and increases tau levels. We show that the Aβ-induced effects on tau were rescued by restoring CHIP levels. Our findings have profound clinical implications as they indicate that preventing Aβ accumulation will significantly alter AD progression. These data highlight the critical role CHIP plays as a link between Aβ and tau and identify CHIP as a new potential target not only for AD but for other neurodegenerative disorders characterized by tau accumulation. ER -