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

Marples, Brian; McGee, Mackenzie; Callan, Sean P.; Bowen, Scott E.; Thibodeau, Bryan J.; Michael, Daniel B.; Wilson, George D.; Maddens, Michael; Fontanesi, James; Martínez, Álvaro

doi:10.1016/j.radonc.2016.01.010

Cited by 21 publications

(31 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it should be noted that irradiation with relatively high doses of X-rays in identical, but older (64 weeks), male APP/PSEN1 TG mice was reported to have short-term beneficial effects on WM endpoints (and amyloidosis) in a recent study [ 73 ], but the potential molecular mechanisms of such beneficial effects were not elucidated. Similarly, one clinical case report described beneficial effects of repeated CT scans on the cognitive state of a patient with advanced AD, but potential protective mechanisms have not been identified [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

“…Counterintuitively, the identical strain of TG mouse was recently used to demonstrate a beneficial effect of photon radiation on AD-type neurodegeneration and behavioral decrements. However, the authors used low LET radiation at relatively high doses (X-rays, ~10 Gy), well above those expected during space travel, and they only investigated short post-irradiation time periods [ 73 ]. None of the studies included wild-type (WT) counterparts in the experimental design, which limited the data interpretation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

et al. 2017

View full text Add to dashboard Cite

Space radiation represents a significant health risk for astronauts. Ground-based animal studies indicate that space radiation affects neuronal functions such as excitability, synaptic transmission, and plasticity, and it may accelerate the onset of Alzheimer’s disease (AD). Although protons represent the main constituent in the space radiation spectrum, their effects on AD-related pathology have not been tested. We irradiated 3 month-old APP/PSEN1 transgenic (TG) and wild type (WT) mice with protons (150 MeV; 0.1–1.0 Gy; whole body) and evaluated functional and biochemical hallmarks of AD. We performed behavioral tests in the water maze (WM) before irradiation and in the WM and Barnes maze at 3 and 6 months post-irradiation to evaluate spatial learning and memory. We also performed electrophysiological recordings in vitro in hippocampal slices prepared 6 and 9 months post-irradiation to evaluate excitatory synaptic transmission and plasticity. Next, we evaluated amyloid β (Aβ) deposition in the contralateral hippocampus and adjacent cortex using immunohistochemistry. In cortical homogenates, we analyzed the levels of the presynaptic marker synaptophysin by Western blotting and measured pro-inflammatory cytokine levels (TNFα, IL-1β, IL-6, CXCL10 and CCL2) by bead-based multiplex assay. TG mice performed significantly worse than WT mice in the WM. Irradiation of TG mice did not affect their behavioral performance, but reduced the amplitudes of population spikes and inhibited paired-pulse facilitation in CA1 neurons. These electrophysiological alterations in the TG mice were qualitatively different from those observed in WT mice, in which irradiation increased excitability and synaptic efficacy. Irradiation increased Aβ deposition in the cortex of TG mice without affecting cytokine levels and increased synaptophysin expression in WT mice (but not in the TG mice). Although irradiation with protons increased Aβ deposition, the complex functional and biochemical results indicate that irradiation effects are not synergistic to AD pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Next, we investigated the relationship between RT and amyloid plaque accumulation. Few studies have reported that RT affects Aβ deposition (16)(17)(18). However, these studies examined the therapeutics effects of RT in AD after LMD-CDRT, and not LD-LDRT.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, patients with AD have been reported to have partially restored cognition, speech, memory, movement and appetite after several brain CT scan exposures (15). Recently, several preclinical studies have revealed a signi cant reduction of amyloid plaque burden and/or tau staining in mouse models of AD with relatively low-moderate total doses of 9-10 Gy in 5 fractions (16)(17)(18)(19) . The RT dose in these studies was a relatively low total dose of 10 Gy, which was lower than the 60 Gy generally used in cancer treatment, but the dose per fraction remained the same as the conventional dose RT (1.8-2 Gy).…”

mentioning

confidence: 99%

Modulation of Neuroinflammation by Low-dose Radiation Therapy in an Animal Model of Alzheimer’s Disease 

Yang

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Recently, several studies have reported that low dose radiation therapy (RT) reduces the release of pro-inflammatory cytokines in inflammatory-degenerative disorders including Alzheimer’s disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Thus, low dose RT is expected to be used clinically for treating AD. However, the proper doses, effects, and underlying mechanisms of RT in AD have not been determined. Therefore, in this study, we aimed to determine the appropriate RT dose and schedule for AD treatment, and to investigate the therapeutic effects and mechanisms of low-dose RT in AD. MethodsWe first determined the proper dose and schedule of RT in late stage AD using 8–9-month old 5x familial AD(5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with a low dose per fraction (LD-LDRT, 5 × 0.6 Gy) and a low-moderate total dose with a conventional dose per fraction (LMD-CDRT, 5 × 2 Gy). ResultsLD-LDRT and LMD-CDRT were found to reduce the level of pro-inflammatory cytokines, i.e. CD54, IL-3, CXCL9/10, and CCL2/4 in the hippocampus of 5xFAD mice. Further, increased microgliosis assessed with Iba-1 was significantly reduced by LD-LDRT in the hippocampus of 5xFAD mice. Moreover, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in 5xFAD mice and attenuated their cognitive impairment; these effects persisted for nearly one month. ConclusionsThe present study showed that LD-LDRT rescues cognitive impairment and prevents accumulation of amyloid plaques by regulating neuroinflammation in the late stage of AD, with an efficacy equivalent to that of LMD-CDRT. Furthermore, it suggests that LD-LDRT may facilitate accessible and convenient treatment in clinical trials compared to LMD-CDRT.

show abstract

“…Yet some investigators believe that external beam radiation treatment of AD holds promise [9]. Cranial irradiation of a mouse AD model reduced beta amyloid plaques in the brain and improved cognitive functioning [10]. An 81-year-old woman with AD improved after 5 computer tomographic scans of the brain, about 40 mGy irradiation each, over a period of 3 months [11].…”

Section: Introductionmentioning

confidence: 99%

Association of Radon Background and Total Background Ionizing Radiation with Alzheimer’s Disease Deaths in U.S. States

Lehrer

Rheinstein²,

Rosenzweig

2017

JAD

View full text Add to dashboard Cite

show abstract

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

Cited by 21 publications

References 5 publications

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

Modulation of Neuroinflammation by Low-dose Radiation Therapy in an Animal Model of Alzheimer’s Disease

Association of Radon Background and Total Background Ionizing Radiation with Alzheimer’s Disease Deaths in U.S. States

Contact Info

Product

Resources

About

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

Cited by 21 publications

References 5 publications

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease – Implications for space travel

Modulation of Neuroinflammation by Low-dose Radiation Therapy in an Animal Model of Alzheimer’s Disease&nbsp;

Association of Radon Background and Total Background Ionizing Radiation with Alzheimer’s Disease Deaths in U.S. States

Contact Info

Product

Resources

About

Modulation of Neuroinflammation by Low-dose Radiation Therapy in an Animal Model of Alzheimer’s Disease