Low-Dose Radiation Therapy Impacts Microglial Inflammatory Response without Modulating Amyloid Load in Female...

Area of Science:

• Neuroscience
• Oncology
• Gerontology

Background:

• Low-dose radiation therapy (LD-RT) exhibits anti-amyloid and anti-inflammatory properties relevant to Alzheimer's disease (AD).
• Previous studies on LD-RT for AD have shown significant heterogeneity in treatment protocols and outcomes.
• Our prior research indicated LD-RT reduced amyloid peptides and inflammation in male TgF344-AD (TgAD) mice.

Purpose of the Study:

• To investigate the efficacy of LD-RT in female TgF344-AD (TgAD) mice, considering the known sex-based differences in AD.
• To determine if LD-RT benefits observed in males extend to females at the same age.

Main Methods:

• Female TgAD mice received bilateral LD-RT with varying fractionation schedules: daily 2 Gy×5, weekly 2 Gy×5, or twice-weekly 1 Gy×10.
• Amyloid load and neuroinflammation markers were assessed using immunohistochemistry and biochemical analyses.

Main Results:

• Daily LD-RT (2 Gy×5) reduced microglial-mediated inflammation but did not impact amyloid load in female TgAD mice.
• Altered fractionation schedules (weekly 2 Gy×5 or twice-weekly 1 Gy×10) showed no significant effect on amyloid or neuroinflammation in females.
• These results contrast with findings in male TgAD mice, where LD-RT reduced both amyloid and inflammation.

Conclusions:

• Daily LD-RT appears to be the most effective fractionation for targeting AD pathology, particularly neuroinflammation, in female mice.
• The anti-amyloid and anti-inflammatory effects of LD-RT may involve distinct mechanisms.
• Sex-specific responses to LD-RT in AD necessitate careful consideration in clinical trial design and interpretation.