title: Imaging the Abeta-related neurotoxicity of Alzheimer disease.
abstract: BACKGROUND
  Neurotoxicity related to the Abeta peptide is thought to be a primary mechanism of dysfunction in Alzheimer disease (AD). Although numerous imaging studies have observed brain dysfunction in AD, whether these imaged defects reflect Abeta-related neurotoxicity remains unknown.
  
  
  OBJECTIVE
  To study Abeta-related neurotoxicity by means of functional imaging maps of the hippocampal formation in human patients and mouse models.
  
  
  METHODS
  Cross-sectional study comparing humans with AD and control subjects, cross-sectional study of J20 mice, a transgenic mouse model of AD, and a longitudinal study of flurbiprofen administration to transgenic mice.
  
  
  METHODS
  Alzheimer disease research center. Subjects Eleven subjects with probable Alzheimer disease and 11 age-matched controls, plus J20 mice and wild-type littermates.
  
  
  METHODS
  In the first study, human subjects and controls underwent magnetic resonance imaging. In the second study, mice underwent imaging at 3, 6, 12, 15, and 21 months of age, for a total of 57 imaging experiments. In the third study, 12 J20 mice underwent imaging repeatedly over time; 6 received flurbiprofen to ameliorate Abeta-related neurotoxicity and 6 received vehicle control.
  
  
  METHODS
  Comparison of hippocampal functional maps.
  
  
  RESULTS
  Among all hippocampal subregions, the entorhinal cortex was the dominant site of dysfunction observed in both human patients and J20 mice. Long-term administration of flurbiprofen rescued entorhinal cortex dysfunction in transgenic mice.
  
  
  CONCLUSIONS
  Our results establish that the neurotoxicity related to the Abeta peptide can be captured in vivo by functional imaging and suggest hippocampal subregions most vulnerable to its toxic effects.
authors.affiliation: Department of Neurology, Robert S. Furchgott Center for Neural and Behavioral Sciences, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Moreno
authors.forename: William E
authors.initials: WE
authors.lastname: Wu
authors.forename: Thomas
authors.initials: T
authors.lastname: Lee
authors.forename: Adam
authors.initials: A
authors.lastname: Brickman
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.forename: Truman R
authors.initials: TR
authors.lastname: Brown
authors.forename: Scott A
authors.initials: SA
authors.lastname: Small
mesh_terms: D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001810:Blood Volume / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D003430:Cross-Sectional Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D018891:Dentate Gyrus / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology / Q000502:physiology; D005480:Flurbiprofen / Q000627:therapeutic use; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen