Radiotherapy in Alzheimer's Disease: A Systematic Review

Background Pathophysiological hallmarks of Alzheimer's Disease (AD) include extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs). Recent studies also demonstrated a role of neuroinflammation in the progression of the disease. Clinical trials and animal studies using low-dose radiation therapy (LDRT) have shown therapeutic potential for AD. This systematic review summarizes the current evidence on the use of LDRT for the treatment of AD, outlines potential mechanisms of action and discusses current challenges in the planning of future trials. Methods A systematic review of human and animal studies as well as registered clinical trials describing outcomes for RT in the treatment of AD was conducted. We followed the 2020 PRISMA guidelines. Articles published until July 1st, 2023, were included. Results The initial search yielded 993 articles. After the removal of duplicates and ineligible publications, a total of 16 (12 animal, 4 human) studies were included. Various dose regimens were utilized in both animal and human trials. The results revealed that LDRT reduced the number of amyloid plaques and NFTs, and has a role in the regulation of genes and protein expression involved in the pathological progression of AD. LDRT has demonstrated reduced astro- and microgliosis, anti-inflammatory and neuroprotective effects and an alleviation of the symptoms of cognitive deficits in animal models. Most studies in humans suggested improvements in cognition and behavior. None of the trials or studies described significant (> grade 2) toxicity. Conclusion Preclinical studies, animal studies, and early clinical trials in humans have shown a promising role of LDRT in the treatment of AD pathologies, although the underlying mechanisms are yet to be fully explored. Phase I/II/III trials are needed to assess the long-term safety, efficacy, and optimal treatment parameters of LDRT in AD treatment.