Cambridge, Mass.– A newly published review in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association offers a comprehensive look at how repetitive transcranial magnetic stimulation (rTMS) could play a transformative role in the treatment of Alzheimer’s disease. Authored by leading neuroscientists and co-founders of Sinaptica Therapeutics, the paper underscores rTMS as a scientifically grounded, non-invasive therapy capable of inducing wide-ranging biological and functional changes in the brain.
The publication, titled “The Neurobiological Foundation of Effective Repetitive Transcranial Magnetic Brain Stimulation in Alzheimer’s Disease,” draws on preclinical models, clinical trials, and neuroimaging data to explain how rTMS influences Alzheimer’s-related pathways. The authors suggest that rTMS doesn’t merely alleviate symptoms—it may actually modify the course of the disease by targeting its underlying mechanisms.
“rTMS has the potential to restore neural network balance and improve plasticity by acting across molecular, synaptic, and network levels,” said Dr. Giacomo Koch, Sinaptica co-founder and neurologist at the Santa Lucia Foundation and University of Ferrara. “This includes enhancing neurotrophic factors like BDNF, modulating neurotransmitter systems, and reducing inflammation and protein buildup associated with Alzheimer’s pathology.”
The paper identifies several therapeutic effects of rTMS, including reduced neuroinflammation, improved synaptic function, potential reduction of amyloid and tau pathology, and enhanced glymphatic clearance of toxic proteins. Collectively, these changes may reestablish long-term potentiation (LTP)-like neuroplasticity and restore connectivity across key brain networks, particularly the Default Mode Network (DMN), which is commonly disrupted in Alzheimer’s patients.
The research team includes experts from institutions such as Harvard Medical School, Sorbonne University, and Massachusetts General Hospital. Dr. Emiliano Santarnecchi, co-author and co-founder of Sinaptica, emphasized that the therapy goes beyond surface-level stimulation: “This is about using targeted, precision neuromodulation to rewire disease-affected circuits. It’s a scalable and safe platform that could become central to Alzheimer’s care.”
The findings build on previous Phase 1 and 2 trials where neuronavigated rTMS protocols showed promise in boosting memory, stabilizing cognition, and improving brain activity in patients with mild to moderate Alzheimer’s disease. The review strengthens the case for incorporating rTMS into a personalized treatment framework, potentially in combination with other therapies.
“This paper represents a paradigm shift in how we understand and approach brain stimulation therapies,” said Sinaptica CEO Ken Mariash. “It validates the science behind our nDMN therapy and supports our mission to deliver systems-level solutions for one of the world’s most urgent health challenges.”
As the global burden of Alzheimer’s continues to rise, the publication provides a compelling roadmap for integrating rTMS into future clinical strategies—anchored not just in symptom management, but in network-level repair and restoration.
