scholarly journals Clinical Approach of Low-Dose Whole-Brain Ionizing Radiation Treatment in Alzheimer’s Disease Dementia Patients

2021 ◽  
pp. 1-1
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ionizing Radiation ◽  
Low Dose ◽  
Radiation Treatment ◽  
Clinical Approach ◽  
Whole Brain ◽  
Dementia Patients ◽  
Alzheimer’S Disease Dementia

scholarly journals Clinical Approach of Low-Dose Whole-Brain Ionizing Radiation Treatment in Alzheimer’s Disease Dementia Patients

2021 ◽  
pp. 1-7
Author(s):  
Mijoo Chung ◽  
Weon Kuu Chung
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Inflammatory Cytokine ◽  
Low Dose ◽  
Transforming Growth Factor ◽  
Amyloid Β ◽  
Clinical Results ◽  
Clinical Approach ◽  
Alzheimer’S Disease Dementia

Our research team recently published two relevant papers. In one study, we have seen the acute effect of low-dose ionizing irradiation (LDIR) did not reduce the amyloid-β (Aβ) protein concentration in brain tissue, yet significantly improved synaptic degeneration and neuronal loss in the hippocampus and cerebral cortex. Surprisingly, in another study, we could see late effect that the LDIR-treated mice showed significantly improved learning and memory skills compared with those in the sham group. In addition, Aβ concentrations were significantly decreased in brain tissue. Furthermore, the pro-inflammatory cytokine tumor necrosis factor-α was decreased and the anti-inflammatory cytokine transforming growth factor-β was increased in the brain tissue of 5xFAD mice treated with LDIR. Definitive clinical results for the safety and efficacy of LDIR have not yet been published and, despite the promising outcomes reported during preclinical studies, LDIR can only be applied to patients with Alzheimer’s disease dementia when clinical results are made available. In addition, in the case of LDIR, additional large-scale clinical studies are necessary to determine the severity of Alzheimer’s disease dementia, indications for LDIR, the total dose to be irradiated, fraction size, and intervals of LDIR treatment. The purpose of this review is to summarize the mechanism of LDIR based on existing preclinical results in a way that is useful for conducting subsequent clinical research.

P4-368: Does a single low dose of ionizing radiation induce Alzheimer's disease-like alterations in mice?

2012 ◽  
Vol 8 (4S_Part_21) ◽  
pp. S787-S787
Author(s):  
Bing Wang ◽  
Kaoru Tanaka ◽  
Bin Ji ◽  
Maiko Ono ◽  
Yaqun Fang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ionizing Radiation ◽  
Low Dose

scholarly journals Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer's disease models

Biology Open ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. bio036657 ◽  
Author(s):  
Soojin Hwang ◽  
Haemin Jeong ◽  
Eun-Hee Hong ◽  
Hae Mi Joo ◽  
Kyoung Sang Cho ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Ionizing Radiation ◽  
Low Dose ◽  
Disease Models

scholarly journals Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4532 ◽  
Author(s):  
Sujin Kim ◽  
Hyunju Chung ◽  
Han Ngoc Mai ◽  
Yunkwon Nam ◽  
Soo Jung Shin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ionizing Radiation ◽  
Cognitive Deficits ◽  
Low Dose ◽  
Memory Loss ◽  
M2 Polarization ◽  
Phenotype Switching ◽  
5Xfad Mice ◽  
The Brain

Alzheimer’s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aβ deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aβ pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aβ deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aβ accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aβ-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aβ deposition and memory loss.

scholarly journals Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hee Jin Kim ◽  
Kyung Rae Cho ◽  
Hyemin Jang ◽  
Na Kyung Lee ◽  
Young Hee Jung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Stem Cells ◽  
Low Dose ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Observation Study ◽  
Serious Adverse Events ◽  
Alzheimer’S Disease Dementia

Abstract Backgrounds Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. Objectives We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs). Methods We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. Results After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. Conclusions Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. Trial registration ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017

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