title: Codistribution of amyloid beta plaques and spongiform degeneration in familial Creutzfeldt-Jakob disease with the E200K-129M haplotype.
abstract: BACKGROUND
  Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid beta (Abeta) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation.
  
  
  OBJECTIVE
  To characterize a family with CJD in which Abeta plaques codistribute with spongiform degeneration.
  
  
  METHODS
  Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.
  
  
  METHODS
  Alzheimer disease research center.
  
  
  METHODS
  Two generations of a family.
  
  
  METHODS
  Clinical, biochemical, and neuropathologic observations in 2 generations of a family.
  
  
  RESULTS
  In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Abeta plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Abeta plaques were present in the APOE epsilon4 carrier but not in the APOE epsilon4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children.
  
  
  CONCLUSIONS
  To our knowledge, this is the first description of Abeta plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Abeta formation and that Abeta pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrP(E200K) may result in increased Abeta deposition.
authors.affiliation: Department of Neurology and Alzheimer's Disease Research Center, Washington University School of Medicine, 4488 Forest Park Ave, Ste 101, St Louis, MO 63108, USA. ghoshaln@neuro.wustl.edu
authors.forename: Nupur
authors.initials: N
authors.lastname: Ghoshal
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.forename: Richard Justin
authors.initials: RJ
authors.lastname: Perrin
authors.forename: S Andrew
authors.initials: SA
authors.lastname: Josephson
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.forename: John Carl
authors.initials: JC
authors.lastname: Morris
mesh_terms: D017668:Age of Onset; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology*; D019286:Endopeptidase K / Q000737:chemistry; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D019286:Endopeptidase K