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Radiother Oncol. 2016 Jan;118(1):43-51. doi: 10.1016/j.radonc.2015.10.019. Epub 2015 Nov 23.

Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).

Author information

1
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA. Electronic address: BRIAN.MARPLES@BEAUMONT.EDU.
2
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
3
Department of Psychology, Wayne State University, Detroit, USA.
4
Beaumont BioBank and Erb Family Core Molecular Laboratories, William Beaumont Hospital, Royal Oak, USA.
5
Beaumont Neurosurgery, William Beaumont Hospital and Michigan Head and Spine Institute, Royal Oak, USA.
6
Division of Geriatric Medicine, William Beaumont Hospital and Department of Internal Medicine, Oakland University-William Beaumont School of Medicine, Royal Oak, USA.

Abstract

BACKGROUND AND PURPOSE:

To investigate if cranial X-irradiation reduces amyloid-β (Aβ) plaques and influences cognitive function in a transgenic mouse model of AD.

METHODS AND MATERIALS:

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).

CONCLUSION:

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.

KEYWORDS:

Amyloid-β; Murine model; Plaque clearance; Radiation

PMID:
26615717
DOI:
10.1016/j.radonc.2015.10.019
[Indexed for MEDLINE]

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