title: Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice.
abstract: Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid β 1-40 peptide levels, and a 34% decrease in insoluble amyloid β 1-42 peptide. Assessment of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD.
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Kalani
authors.initials: K
authors.lastname: Ruberu
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Sonia Sanz
authors.initials: SS
authors.lastname: Muñoz
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jenner
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Adena
authors.initials: A
authors.lastname: Spiro
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Laboratoire de biologie moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Canada; BioMed, centre de recherches biomédicales, Université du Québec à Montréal, Montréal, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Rassart
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología - Instituto de Biología y Genética Molecular, Universidad de Valladolid - CSIC, Valladolid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Sanchez
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología - Instituto de Biología y Genética Molecular, Universidad de Valladolid - CSIC, Valladolid, Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Ganfornina
authors.affiliation: Neuroscience Research Australia, Randwick, NSW, Australia; School of Medical Sciences, University of New South Wales, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Karl
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; School of Biological Sciences, University of Wollongong, NSW, Australia. Electronic address: brettg@uow.edu.au.
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D053399:Apolipoproteins D / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D016564:Amyloid beta-Protein Precursor; D053399:Apolipoproteins D; D020890:Neuregulin-1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer's disease; Amyloid pathology; Amyloid β; Apolipoprotein D; Neurodegeneration