title: Low-density lipoprotein receptor-related protein is decreased in optic neuropathy of Alzheimer disease.
abstract: BACKGROUND
  Alzheimer disease (AD) is associated with optic nerve degeneration, yet the underlying pathophysiology of this disease and the optic nerve disorder remain poorly understood. Low-density lipoprotein receptor-related protein (LRP) is implicated in the pathogenesis of AD by mediating the transport of amyloid-β (Aβ) out of the brain into the systemic circulation. As a key player in the reaction to central nervous system injury, astrocytes associate with LRP in AD. This study investigates the role of LRP and astrocytes in the pathogenesis of AD optic neuropathy.
  
  
  METHODS
  To investigate the role of LRP and astrocytes in the pathogenesis of AD optic neuropathy, we conducted immunohistochemical studies on postmortem optic nerves in AD patients (n = 11) and age-matched controls (n = 10) to examine the presence of LRP. Quantitative analyses using imaging software were used to document the extent of LRP in neural tissues. Axonal integrity was assessed by performing immunohistochemistry on the subjects' optic nerves with an antibody to neurofilament (NF) protein. Double-immunofluorescence labeling was performed to investigate whether LRP colocalized with astrocytes, expressing glial fibrillary acidic protein.
  
  
  RESULTS
  LRP expression was decreased in AD optic nerves compared to that in controls (P < 0.001). LRP immunoreactivity was observed in the microvasculature and perivascularly in close proximity to the astrocytic processes. Colocalization of LRP in the astrocytes of optic nerves was also demonstrated. The presence of optic neuropathy was confirmed in the AD optic nerves by demonstrating greatly reduced immunostaining for NF protein as compared to controls.
  
  
  CONCLUSIONS
  The reduction of LRP in the AD degenerative optic nerves supports the hypothesis that LRP may play a role in the pathophysiology of AD optic neuropathy.
authors: Department of Ophthalmology, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-0228, USA.
authors: Lloyd M
authors: LM
authors: Cuzzo
authors: Fred N
authors: FN
authors: Ross-Cisneros
authors: Kenneth M
authors: KM
authors: Yee
authors: Michelle Y
authors: MY
authors: Wang
authors: Alfredo A
authors: AA
authors: Sadun
references: J Neuroophthalmol. 2006 Mar;26(1):18-24
references: 16518161
references: FEBS Lett. 1994 Feb 7;338(3):301-5
references: 8307199
references: J Clin Invest. 2000 Nov;106(9):1159-66
references: 11067868
references: Metab Pediatr Syst Ophthalmol (1985). 1989;12(1-3):64-8
references: 2770524
references: Science. 2002 Jul 19;297(5580):353-6
references: 12130773
references: Stroke. 2004 Nov;35(11 Suppl 1):2628-31
references: 15459432
references: Nat Cell Biol. 2009 Feb;11(2):143-53
references: 19098903
references: Cell. 2005 Feb 25;120(4):545-55
references: 15734686
references: Brain Res. 1995 Sep 11;691(1-2):235-8
references: 8590059
references: Prog Drug Res. 2003;61:39-78
references: 14674608
references: Science. 2010 Dec 24;330(6012):1774
references: 21148344
references: Surv Ophthalmol. 1989 Jul-Aug;34(1):31-43
references: 2678551
references: CNS Neurol Disord Drug Targets. 2009 Mar;8(1):16-30
references: 19275634
references: J Neuropathol Exp Neurol. 1997 Oct;56(10):1095-7
references: 9329452
references: Acta Neuropathol. 2009 Jul;118(1):103-13
references: 19319544
references: Neurology. 1991 Apr;41(4):479-86
references: 2011243
references: Semin Ophthalmol. 2003 Jun;18(2):50-7
references: 14566623
references: J Biol Chem. 1997 Sep 19;272(38):23946-51
references: 9295345
references: Acta Neuropathol. 2006 Oct;112(4):405-15
references: 16865397
references: Curr Pharm Des. 2008;14(16):1601-5
references: 18673201
references: Ophthalmology. 1990 Jan;97(1):9-17
references: 2314849
references: J Neurosci. 2004 Apr 28;24(17):4259-65
references: 15115822
references: J Clin Invest. 2000 Dec;106(12):1489-99
references: 11120756
references: Ann Neurol. 1995 Feb;37(2):211-7
references: 7531418
references: Arch Neurol. 2003 Aug;60(8):1119-22
references: 12925369
references: Neuroscience. 1994 Nov;63(2):517-31
references: 7891862
references: Ann N Y Acad Sci. 1994 Sep 10;737:1-13
references: 7524391
references: J Neurochem. 2004 May;89(4):807-11
references: 15140180
references: Science. 2002 Mar 22;295(5563):2264-7
references: 11910111
references: EMBO J. 2002 Nov 1;21(21):5691-700
references: 12411487
references: J Clin Invest. 2002 Nov;110(10):1375-81
references: 12438432
references: Arch Neurol. 2000 May;57(5):646-50
references: 10815129
references: Acta Neuropathol. 2006 Oct;112(4):389-404
references: 16906426
references: Neurotherapeutics. 2008 Jul;5(3):409-14
references: 18625452
references: Ann N Y Acad Sci. 2006 Nov;1086:35-53
references: 17185504
references: Annu Rev Biochem. 2002;71:405-34
references: 12045102
references: Alzheimers Dement. 2010 Mar;6(2):158-94
references: 20298981
references: Curr Alzheimer Res. 2007 Apr;4(2):191-7
references: 17430246
references: J Clin Invest. 2001 Sep;108(6):779-84
references: 11560943
references: Mol Cell Biol. 2004 Oct;24(20):8872-83
references: 15456862
references: Neurodegener Dis. 2006;3(4-5):233-8
references: 17047362
references: J Biol Chem. 2005 May 20;280(20):20140-7
references: 15772078
references: Am J Ophthalmol. 1987 Aug 15;104(2):113-20
references: 3618708
references: Folia Neuropathol. 2005;43(1):1-6
references: 15827884
references: Am J Pathol. 1992 Jul;141(1):37-42
references: 1632469
references: Exp Cell Res. 1999 Sep 15;251(2):433-41
references: 10471328
references: J Neurosci. 2002 Nov 1;22(21):9298-304
references: 12417655
references: Neuron. 2004 Sep 2;43(5):605-8
references: 15339642
references: Neurology. 2000 Jun 13;54(11):2045-54
references: 10851361
references: Neurology. 2006 Nov 28;67(10):1852-4
references: 17130422
references: Neurobiol Aging. 2001 Nov-Dec;22(6):931-6
references: 11755001
references: Acta Neuropathol. 2009 Sep;118(3):381-9
references: 19277685
references: Nat Med. 2007 Sep;13(9):1029-31
references: 17694066
references: N Engl J Med. 1986 Aug 21;315(8):485-7
references: 3736630
references: Drug Discov Today. 2006 Oct;11(19-20):931-8
references: 16997144
references: Curr Opin Cell Biol. 1998 Oct;10(5):667-71
references: 9818179