title: The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features.
abstract: BACKGROUND
  Amyloid-β (Aβ) peptides derive from the amyloid precursor protein (APP) and play a pivotal role in Alzheimer's disease (AD) pathogenesis. Our previous work showed that the APP intracellular domain (AICD), which is produced simultaneously with Aβ, also contributes to the development of AD-like features. Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features. However, the effects of apoE-mimetic treatment on AICD-mediated AD-like pathologies remain to be elucidated.
  
  
  OBJECTIVE
  To study the effects of an apoE mimetic (COG112) on neuroinflammation, hyperphosphorylation of tau and defects in adult neurogenesis in AICD- overexpressing transgenic mice (FeCγ25 line).
  
  
  METHODS
  Beginning at 1 month of age, animals were administered subcutaneous COG112 3 times per week for 3 months, followed by immunohistochemical analysis for neuroinflammation, neurogenesis and phosphorylated tau.
  
  
  RESULTS
  Treatment with COG112 significantly reduced neuroinflammation in AICD mice and protected against impaired adult hippocampal neurogenesis. We also found that COG112 treatment reduced hyperphosphorylation and somatodendritic accumulation of tau in the hippocampus and cerebral cortex of AICD mice.
  
  
  CONCLUSIONS
  Reduction of neuroinflammation by the apoE-mimetic COG112 protects against impaired neurogenesis and tau pathology in AICD transgenic mice. These data suggest that neuroinflammation plays an important role in AICD-induced AD-like pathologies.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. ghosalk@ccf.org
authors.forename: Kaushik
authors.initials: K
authors.lastname: Ghosal
authors.forename: Andrea
authors.initials: A
authors.lastname: Stathopoulos
authors.forename: Dustin
authors.initials: D
authors.lastname: Thomas
authors.forename: David
authors.initials: D
authors.lastname: Phenis
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.forename: Sanjay W
authors.initials: SW
authors.lastname: Pimplikar
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; C530207:COG112 peptide; D010455:Peptides; D016875:tau Proteins