Association of CLU genotype with cerebral amyloid angiopathy

 
   Lead Investigator:    John Fryer
   Institution      :    Mayo Graduate School
   E-Mail           :    Fryer.John@mayo.edu
   Proposal ID      :    627



   Proposal Description:
   The rs11136000 SNP in the intronic region of the Clusterin (CLU) gene is          associated with significantly increased risk for late onset Alzheimer???s         disease (AD). However, it is currently unknown how CLU genotype may alter         neuropathology associated with AD. We and others have found that CLU strongly     immunolabels parenchymal amyloid plaques and amyloid angiopathy. Our              unpublished data using an APP transgenic mouse model of amyloidosis reveals       that mice lacking CLU protein have a striking shift in amyloid pathology from     parenchymal plaques to amyloid angiopathy. We seek to know whether CLU genotype   in humans is associated with amyloid angiopathy (as well as other hallmark        neuropathologies such as Braak plaque and tangle severity). Because APOE4 is a    strong driver of amyloid angiopathy, we will need to account for this.            Additionally, it would be beneficial to show specificity for CLU effects by       also showing that other genes do not have similar effects (e.g. PICALM, BIN1,     CR1, CD33, ABCA1, and ABCA7). Obtaining this data from NACC would allow us to     know whether the effects we see in the mouse model have human relevance or        whether it is simply an artifact of a mouse model.