Analysis of genetic susceptibility loci underlying Alzheimer's disease with
additional feature
 
   Lead Investigator:    Giuseppe Tosto
   Institution      :    Columbia
   E-Mail           :    gt2260@cumc.columbia.edu
   Proposal ID      :    350


   Publications:


1  Tosto G,  Monsell SE, Kukull WS , Mayeux R
   Latent Analysis of Extrapyramidal Signs In Alzheimer Disease Identifies Distinct Disease Expressions
   Abstract  Alzheimers Dement,10:P819,2014,

   PUBLISHED





   Proposal Description:
   Alzheimer disease (AD) is the most common neurodegenerative disease but most studies assess AD as a unique entity without further classifications moreover, considerable confusion still exists concerning its clinical, neuropathological and genetic delineation. Although the main clinical hallmark is progressive loss in cognitive function in particular the memory domain, persons with AD often develop additional features such as visual hallucinations (HA) or extrapyramidal signs (EPS) i.e. symptoms commonly seen in related forms of dementia (Dementia with Lewy Bodies, Parkinson's disease). There is also significant neuropathological overlap between these entities (both Lewy bodies and amyloid pathology occur in all three conditions and are also seen in elderly without AD, DLB or PD). The project will follow a two-step sequential approach. First we'll try to identify of genetic variants that are associated with clinically defined AD plus EPS/HA (Heterogeneity model) or modify the risk of EPS/HA in the presence of AD (Disease modifier model). Subsequently, we'll try to identify NP hallmarks (i.e. Plaques, neurofibrillary tangles, Lewy Bodies) associated with genetic variants outlined in previous steps. We anticipate that disentangling the genetic variation underlying AD with HA or EPS will help elucidate the complex disease etiology identifying novel targets for prevention, treatment and diagnostic testing.