title: Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).
abstract: OBJECTIVE
  To investigate if cranial X-irradiation reduces amyloid-β (Aβ) plaques and influences cognitive function in a transgenic mouse model of AD.
  
  
  METHODS
  B6.Cg-Tg (APPswePSEN1dE9)85Dbo/J AD-prone mice were given cranial X-irradiation. The number of Aβ plaques, along with expression of AD specific genes (84 genes: Mouse Alzheimer's Disease RT(2) Profiler), radiation-associated cytokines (Milliplex MAP Mouse Cytokine Chemokine Immunoassay) and immunohistochemistry (IL10, IL-1β, Iba1 CD45) was assessed. Behavioral testing was performed to relate changes in Aβ burden to cognitive function using a Morris water-maze task.
  
  
  RESULTS
  Single X-ray doses reduced the number (p=0.002) and size (p=0.01) of Aβ plaques. Low-dose fractionation produced greater 50.6% (1 Gy × 10), 72% (2 Gy × 5) and 78% (2 Gy × 10) reductions. Irradiation was associated with gene (Pkp4, 1.5-fold, p=0.004) and proteomic (MIP-2, 8-fold, p=0.0024) changes at 24-48 h. Microglia increased at 4 weeks post-irradiation (p=0.001). The reduction in Aβ burden (2 Gy × 5) was associated with cognitive improvement (p=0.012).
  
  
  CONCLUSIONS
  This is the first report that a clinically relevant course of external beam irradiation (2 Gy × 5) produces a significant reduction in AD-associated amyloid-β plaques with a subsequent improvement in cognitive function. However, longer-term studies are needed to define the precise underlying mechanism and longevity of this response.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA. Electronic address: BRIAN.MARPLES@BEAUMONT.EDU.
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: McGee
authors.affiliation: Department of Psychology, Wayne State University, Detroit, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Callan
authors.affiliation: Department of Psychology, Wayne State University, Detroit, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Bowen
authors.affiliation: Beaumont BioBank and Erb Family Core Molecular Laboratories, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Thibodeau
authors.affiliation: Beaumont Neurosurgery, William Beaumont Hospital and Michigan Head and Spine Institute, Royal Oak, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Michael
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.affiliation: Division of Geriatric Medicine, William Beaumont Hospital and Department of Internal Medicine, Oakland University-William Beaumont School of Medicine, Royal Oak, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Maddens
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: James
authors.initials: J
authors.lastname: Fontanesi
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Martinez
mesh_terms: D000544:Alzheimer Disease / Q000532:radiotherapy*; D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects*; D001921:Brain / Q000528:radiation effects*; D003071:Cognition / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000379:methods*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000532:radiotherapy*
keywords: Amyloid-β; Murine model; Plaque clearance; Radiation