Do AD risk loci other than APOE improve diagnostic accuracy of MCI and PRAD
with respect to a primary neuropathological diagnosis of AD
 
   Lead Investigator:    Alberto Serrano-Pozo
   Institution      :    Univ of Iowa
   E-Mail           :    aserrano1@mgh.harvard.edu
   Proposal ID      :    680



   Proposal Description:
   The clinical construct of mild cognitive impairment (MCI) is pathologically heterogeneous, with only around half of subjects with MCI diagnosis having significant Alzheimer disease neuropathological change, up to 25 mixed pathologies, and up to 25 no underlying neuropathological diagnosis, according to the Religious Orders Study/Rush Memory and Aging Project study. The same applies to the clinical construct of probable Alzheimer disease (PRAD) because up to 16 to 30 of subjects diagnosed with PRAD in an AD center have insufficient AD neuropathological change at autopsy. We asked whether AD risk loci other than APOE may be helpful to improve the diagnostic accuracy of the clinical diagnoses of MCI and PRAD with respect to a primary neuropathological diagnosis of AD. We hypothesized that some of the 21 AD risk loci recently described in a large meta-analysis of GWAS, or a combination thereof, will improve the predictive value of the clinical categories of MCI and PRAD with respect to the presence of significant AD neuropathological change at autopsy (intermediate or high AD neuropathological change by the 2012 NIA-AA criteria). This genetic footprint of AD could be used in clinical trials of disease-modifying drugs to select only MCI and PRAD subjects with underlying AD pathophysiology.??