Antidepressants and amyloid pathology in Alzheimer's disease

 
   Lead Investigator:    Mark Lovell
   Institution      :    University of Kentucky
   E-Mail           :    malove2@email.uky.edu
   Proposal ID      :    655



   Proposal Description:
   Preliminary studies from our laboratory show increased levels of a recently deorphanized g-coupled protein receptor (GPR-39) in vulnerable brain regions of Alzheimer???s disease (AD) and preclinical AD (PCAD) patients but not those with Diffuse Lewy Body disease or Frontotemporal Dementia compared to age matched control subjects. ??In vitro data show treatment of H4 neuroglioma cultures with a GPR-39 agonist leads to an upregulation of the protein that correlates with increased amyloid beta peptide production. ??Our data also show treatment with a GPR-39 antagonist leads to decreased A?? production. ??Recent studied in the literature show treatment of rats with specific antidepressants leads to significant increases in levels of GPR-39. Because older patients are often prescribed antidepressants, we propose to use the longitudinal UDS database and the Neuropathology database to determine if use of specific categories of antidepressants is associated with increased A?? pathology among autopsied participants or with an increased rate of progression to dementia. We propose to examine frequency of diffuse and neuritic plaques among users and nonusers or specific antidepressant classes, and we propose to examine the probability of transition to dementia from intact cognition and mild cognitive impairment in users and nonusers. Findings from this study may identify potential factors that account for accelerated pathology in AD.