%0 Journal Article
%T 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
%A Guilian Xu
%A Cameron C Green
%A Susan E Fromholt
%A David R Borchelt
%J Alzheimer's Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/alzrt110
%X 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 A¦Â accumulation.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 A¦Â40/42 accumulation, or the architecture of amyloid plaques when LRP1 levels were reduced.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.Amyloid deposition is a key pathological event in Alzheimer's disease. A large body of evidence suggests that low density lipoprotein (LDL) receptor related protein (LRP1), may be a key mediator of amyloid deposition. As a member of the LDL receptor family, LRP1 is a large, multifunctional, endocytic receptor that is highly expressed in neurons (reviewed by Andersen [1]), activated astrocytes [2-4], and microglia [5]. Direct binding of LRP1 to the amyloid precursor protein (APP) has been shown to affect endoproteolytic processing of APP to increase the production of A¦Â42 peptides [6], which are the major constituent of amyloid deposits [7]. LRP1 can promote A¦Â production by altering the processing of APP through interactions via the Kunitz
%U http://alzres.com/content/4/2/12