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Basic Science and Pathogenesis.

Jennifer Fazzari1, Jarred Nesbitt1, Eugenia Trushina1

  • 1Mayo Clinic, Rochester, MN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Minibeam radiation therapy (MBRT) shows promise for Alzheimer's disease (AD) by reducing amyloid plaques. This novel approach may offer a safer alternative to conventional radiation for AD treatment.

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Area of Science:

  • Neuroscience
  • Radiation Oncology
  • Pharmacology

Background:

  • Alzheimer's disease (AD) requires new treatments targeting its complex pathogenesis.
  • Current therapies offer limited benefits by addressing single disease hallmarks.
  • Low-dose whole brain radiation shows potential in AD models but carries risks like vascular damage.

Purpose of the Study:

  • To investigate Minibeam Radiation Therapy (MBRT) as a potentially safer and effective strategy for AD.
  • To evaluate MBRT's ability to target amyloid deposition, neuroinflammation, and brain energy metabolism.
  • To reduce overall radiation exposure to the brain while addressing AD hallmarks.

Main Methods:

  • Developing an MBRT treatment paradigm for AD hallmarks.
  • Irradiating 5XFAD mice with MBRT (2 Gy peak, 0.3 Gy valley) or conventional 2 Gy radiation.
  • Assessing amyloid beta levels, plaque burden, and cognitive function (Y-maze) 4 weeks post-irradiation.

Main Results:

  • Preliminary trends indicated reductions in insoluble amyloid beta (Aβ) in MBRT-treated mice.
  • No significant cognitive decline was observed in untreated 5XFAD mice at the study age.
  • Further analysis of plaque burden and cognitive function is ongoing.

Conclusions:

  • MBRT demonstrates potential in reducing amyloid pathology in an AD mouse model.
  • Further studies are needed to optimize MBRT parameters for AD treatment.
  • Future research will focus on MBRT efficacy after cognitive deficits onset.