{"doi":"10.4103/1673-5374.366499","title":"Transcranial photobiomodulation with near-infrared light: a promising therapeutic modality for Alzheimer’s disease","abstract":"Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique that delivers near-infrared (NIR) light with low irradiance (i.e., power density in mW/cm2) in the wavelength range of 800–1070 nm. Several recently published books or collected literature (Hamblin, 2019; Gonzalez-Lima, 2021) and papers (Nizamutdinov et al., 2022) offer comprehensive reviews of the mechanism of action and potential clinical translations of tPBM for the treatment of a variety of diseases, including neurodegenerative diseases (Alzheimer’s disease (AD), and Parkinson’s disease), traumatic brain injury, stroke, and psychiatric disorders (depression and post-traumatic stress disorder). This communication focuses on the feasibility and benefits of tPBM in treating patients with AD. The socio-economic burden of AD is significant and will only increase with longer life expectancy unless effective interventions are developed. Currently, none of the therapeutic strategies have been successful in treating or alleviating the symptoms of AD. In this paper, we review the well-accepted tPBM mechanisms of action, and summarize key experimental findings of tPBM-induced neurophysiological enhancement (Wang et al., 2017, 2021; Shahdadian et al., 2022; Truong et al., 2022) and behavioral improvements in healthy young (Zhao, 2022) and older adults (Qu et al., 2022), and provide tPBM mechanistic insights in living human brains. In addition, we demonstrate our clinical study with evidence-based safety and cognitive improvements in patients with dementia using daily tPBM therapeutic protocol at home (Nizamutdinov et al., 2021). Finally, we also discuss the mechanistic rationale of tPBM supported by a recent AD animal study (Yang et al., 2022) and documented literature. Mechanism of action of PBM: The most well-documented and accepted mechanism underlying the effects of PBM is based on the reports that complex IV of cytochrome C oxidase (CCO) in the mitochondrial respiratory chain can absorb NIR light at the local stimulation site (Wang et al., 2017; Hamblin, 2019; Gonzalez-Lima, 2021). The absorbed light stimulates cellular adenosine triphosphate, manages or counteracts reactive oxygen species, Ca2+, and the release of nitric oxide (NO) (Hamblin, 2019). Accordingly, this signaling reaction promotes energy supplementation to the disease-affected brain tissue with prominent mitochondrial dysfunction. Another reported mechanism contributing to the local restoration of brain functionality is vasodilation stimulated by the endothelial secretion of NO with subsequent regional elevated blood perfusion resulting in increased cortical oxygenation. This mechanism contributes to oxidative stress management and supports other reported effects of tPBM, including neuroprotection, neurogenesis, synaptogenesis, and angiogenesis. Engaged signaling cascades and corresponding changes in the brain parenchyma promote positive support of energy metabolism and neuron-to-neuron communication networks, enhancing brain clearance through the improved local function of the vascular, glymphatic, and lymphatic systems (Nizamutdinov et al., 2022). Overall, tPBM intervention improves brain performance in healthy adults and patients affected by chronic neuropathology. Interestingly, local tPBM also triggers a cascade of systemic responses with positive immune and prominent anti-inflammatory outcomes (Nizamutdinov et al., 2022). Significant neurophysiological effects of tPBM on healthy humans: Since 2017, Liu and her group have reported a series of neurophysiological measurements from healthy humans in vivo by quantifying cerebral hemodynamic, metabolic, and electrophysiological responses during and after tPBM on the forehead using a 1064-nm laser stimulation (Wang et al., 2017, 2021; Shahdadian et al., 2022; Truong et al., 2022). These findings offer novel experimental evidence and mechanistic insights into how tPBM affects the living human brain at the site of stimulation, distant, a","journal":"Neural Regeneration Research","year":2023,"id":381658,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":584121,"name":"Damir Nizamutdinov","orcid":"0000-0001-6020-6869","position":1,"is_corresponding":false},{"id":321218,"name":"Jason H. Huang","orcid":"0000-0002-4426-0168","position":2,"is_corresponding":false},{"id":294220,"name":"Hanli Liu","orcid":"0000-0002-9312-5691","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:17:12.933204Z","pmid":"36926713","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}