Neuropathological studies of primary age-related tauopathy: the PART working

 
   Lead Investigator:    Kurt Farrell
   Institution      :    Mount Sinai
   E-Mail           :    kurt.farrell@mssm.edu
   Proposal ID      :    766



   Proposal Description:
   Together with a group of neuropathologists, we have recently established          consensus criteria for a new category of neuropathologic change, termed primary   age-related tauopathy (PART). Individuals with PART display AD-type               neurofibrillary tangles (NFT) in the medial temporal lobe in the absence of A??   plaques. Patients with PART may have normal cognition, amnestic mild cognitive    impairment (aMCI), or an amnestic dementia. Studies suggest that subjects with    PART have molecular and genetic features that provide resistance to cerebral      amyloidosis but also vulnerability to neurofibrillary degeneration. The           long-term goal of the PART working group is to characterize PART to enable new    diagnostic and therapeutic strategies. Our objective is to validate the new       criteria for PART, characterize its molecular signature, and perform a rigorous   genetic analysis. Our hypothesis is that subjects with PART have distinct         characteristics that underlie their NFT+/A??- phenotype. The clinical and         genetic patient data from the NACC study will be compared to the data we are      generating to bolster the following aims:                                         Aim 1. To validate the neuropathological criteria for PART and lay the            groundwork for clinical and mechanistic studies that will elucidate disease       burden, pathogenesis and progression.                                             Aim 2. To test the hypothesis that PART has a genetic risk profile that           overlaps with some aspects of AD genetics (e.g., MAPT haplotypes) but diverges    with respect to others (e.g., APOE genotype).                                     This research has the potential to represent a paradigm shift in AD research by   transforming the way we conceptualize early AD neuropathologic change. By         obtaining this fundamental knowledge, we will pave the way towards a better       understanding of the pathogenesi