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.
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 ADpatients (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: John E Donahue; Stephanie L Flaherty; Conrad E Johanson; John A Duncan; Gerald D Silverberg; Miles C Miller; Rosemarie Tavares; Wentian Yang; Qian Wu; Edmond Sabo; Virginia Hovanesian; Edward G Stopa Journal: Acta Neuropathol Date: 2006-07-25 Impact factor: 17.088
Authors: I Tooyama; T Kawamata; H Akiyama; H Kimura; S K Moestrup; J Gliemann; A Matsuo; P L McGeer Journal: Brain Res Date: 1995-09-11 Impact factor: 3.252
Authors: Heiko Braak; Irina Alafuzoff; Thomas Arzberger; Hans Kretzschmar; Kelly Del Tredici Journal: Acta Neuropathol Date: 2006-08-12 Impact factor: 17.088
Authors: Janey L Wiggs; Brian L Yaspan; Michael A Hauser; Jae H Kang; R Rand Allingham; Lana M Olson; Wael Abdrabou; Bao J Fan; Dan Y Wang; Wendy Brodeur; Donald L Budenz; Joseph Caprioli; Andrew Crenshaw; Kristy Crooks; Elizabeth Delbono; Kimberly F Doheny; David S Friedman; Douglas Gaasterland; Terry Gaasterland; Cathy Laurie; Richard K Lee; Paul R Lichter; Stephanie Loomis; Yutao Liu; Felipe A Medeiros; Cathy McCarty; Daniel Mirel; Sayoko E Moroi; David C Musch; Anthony Realini; Frank W Rozsa; Joel S Schuman; Kathleen Scott; Kuldev Singh; Joshua D Stein; Edward H Trager; Paul Vanveldhuisen; Douglas Vollrath; Gadi Wollstein; Sachiko Yoneyama; Kang Zhang; Robert N Weinreb; Jason Ernst; Manolis Kellis; Tomohiro Masuda; Don Zack; Julia E Richards; Margaret Pericak-Vance; Louis R Pasquale; Jonathan L Haines Journal: PLoS Genet Date: 2012-04-26 Impact factor: 5.917