Repetitive Transcranial Magnetic Stimulation Decreases Serum Amyloid-β and Increases Ectodomain of p75 Neurotrophin Receptor in Patients with Alzheimer’s Disease

Abstract

Background: This study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on serum levels of Amyloid-β (Aβ) as well as the ectodomain of p75 neurotrophin receptor (p75ECD) in patients with Alzheimer's disease (AD). Methods: A total of 46 patients diagnosed with AD between June 1, 2020 and December 31, 2021 were randomized to undergo either 20 Hz rTMS treatment of the left dorsolateral prefrontal cortex (DLPFC) or sham procedure. Cognitive function and activity of daily living were evaluated. Neuropsychological tests and blood samples were gathered at baseline and at 2, 3, 4, and 6 weeks after rTMS therapy. Results: There were no evident differences between rTMS group and sham group in serum Aβ40, Aβ42, total Aβ, ApoE, and p75ECD standards at baseline (p > 0.05). Serum levels of Aβ40, Aβ42, as well as total Aβ, were significantly lower in the rTMS group at 3, 4 and 6 weeks relative to the sham group (p < 0.05). Serum p75ECD levels in the rTMS group were significantly higher than those of the sham group at 3, 4 and 6 weeks (p < 0.05). Levels of serum Aβ40 (r: -0.78, -0.83, -0.68, respectively), Aβ42 (r: -0.76, -0.76, -0.61, respectively) and total Aβ (r: -0.74, -0.81, -0.66, respectively) were negatively correlated with MoCA, MMSE and MBI scores, while serum p75ECD levels (r: 0.84, 0.90, 0.72, respectively) were positively correlated (p < 0.01). The level of serum Aβ40 (r = 0.77), Aβ42 (r = 0.69) as well as total Aβ (r = 0.73) were positively correlated with ADAS-cog score, while p75ECD levels (r = -0.86) were negatively correlated (p < 0.01). Conclusions: The results of this study suggest that rTMS may decrease serum Aβ levels and increase serum p75ECD levels in patients with AD, offering insight into a potential underpinning mechanism of rTMS.

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

“…We found that a 1-month iTBS treatment ameliorates pathologies such as Aβ deposition, neuroinflammation, neuronal, and synaptic loss in the brain of AD mice for at least 2 months, suggesting a long-lasting effect of iTBS on the pathological improvement in AD. These results are consistent with those of our previous clinical study, 47 in which we found that HF-rTMS could reduce the serum Aβ levels for at least 6 weeks in patients with AD. Based on these findings, it is reasonable to propose that rTMS may exert longterm effects by improving key pathologies in the brain of patients with AD.…”

“…To assess the efficacy of this protocol, we conducted a sham‐controlled study on 46 patients with AD, that were randomized to real or sham stimulation groups 47 . The results showed that patients' global cognition and activity of daily living were enhanced significantly by a 6‐week rTMS treatment.…”

Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer’s Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies

“…The intensities in most studies were 90%, 100%, and 120% of the motor threshold. Among the various stimulation sites explored, the dorsolateral prefrontal cortex (DLPFC) emerged as a frequently targeted region across multiple studies [25,43,[51][52][53][54][55][56][57]. Additionally, other targets included the hippocampus [36,58], angular gyrus [59], precuneus [60], cerebellum [61], and regions adjacent to the temporal lobe [34,62].…”