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. 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)

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Cranial Irradiation Significantly Reduces Beta Amyloid Plaques in the Brain and Improves Cognition in a Murine Model of Alzheimer's Disease (AD)

Brian Marples et al. Radiother Oncol. .

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.

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