title: Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice.
abstract: BACKGROUND
  The low-density lipoprotein receptor-related protein (LRP1) and its family members have been implicated in the pathogenesis of Alzheimer's disease. Multiple susceptibility factors converge to metabolic pathways that involve LRP1, including modulation of the processing of amyloid precursor protein (APP) and the clearance of Aβ peptide.
  
  
  METHODS
  We used the Cre-lox system to lower LRP1 levels in hippocampal neurons of mice that develop Alzheimer-type amyloid by crosses between mice that express Cre recombinase under the transcriptional control of the GFAP promoter, mice that harbor loxp sites in the LRP1 gene, and the APPswe/PS1dE9 transgenic model. We compared amyloid plaque numbers in APPswe/PS1dE9 mice lacking LRP1 expression in hippocampus (n = 13) to mice with normal levels of LRP1 (n = 12). Student t-test was used to test whether there were significant differences in plaque numbers and amyloid levels between the groups. A regression model was used to fit two regression lines for these groups, and to compare the rates of Aβ accumulation.
  
  
  RESULTS
  Immunohistochemical analyses demonstrated efficient elimination of LRP1 expression in the CA fields and dentate gyrus of the hippocampus. Within hippocampus, we observed no effect on the severity of amyloid deposition, the rate of Aβ40/42 accumulation, or the architecture of amyloid plaques when LRP1 levels were reduced.
  
  
  CONCLUSIONS
  Expression of LRP1 by neurons in proximity to senile amyloid plaques does not appear to play a major role in modulating the formation of these proximal deposits or in the appearance of the associated neuritic pathology.
authors.affiliation: Department of Neuroscience, SantaFe HealthCare Alzheimer's Disease Center, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Guilian
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neuroscience, SantaFe HealthCare Alzheimer's Disease Center, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA ; Department of Educational Psychology and Learning Systems, College of Education, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Green
authors.affiliation: Department of Neuroscience, SantaFe HealthCare Alzheimer's Disease Center, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Fromholt
authors.affiliation: Department of Neuroscience, SantaFe HealthCare Alzheimer's Disease Center, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt