**1. Introduction**

Photobiomodulation (PBM) is the application of light therapy that utilizes photons to alter the activity of molecular and cellular processes in the tissue where the stimulation is applied [1]. Historical contexts of PBM therapy and its development indicate that this intervention has been synonymous with low level laser therapy (LLLT), intensive monochromatic light energy, and light emitting diode (LED) energy interventions [2–4]. The emission of monochromatic light within the range of 600 to 1000 nm from low level lasers and LEDs is thought to underlie alterations in cellular signaling pathways, as the photons from LLLT interventions can influence ATP synthesis, gene expression, and oxygen consumption [5]. This hypothesis is

based upon the ability of cytochrome c oxidase (CCO), an enzyme within the electron transport chain, to alter mitochondrial membrane potential via exposure to photonic energy in the spectra of 360-860 nm [5]. Near infrared light (NIR) is defined as the emission of light within the 700 to 980 nm spectra whereas infrared light (IR) is energy that is emitted at 1000 nm or 300 GHz and above [6].

While PBM has shown efficacy for neurodegenerative disorders, this intervention has been applied to other neurological disorders which include, but are not limited to, retinal disorders, ischemic stroke, and epilepsy [7]. Neurodegenerative diseases are currently considered as incurable as pharmacological interventions have failed to slow the progression of neuronal necrosis [8–11]. Because many pharmacological interventions induce significant side effects and have largely proven ineffective in curtailing degenerative processes, determining new non-invasive therapies for these disorders is imperative [7]. As the mechanisms by which transcranial PBM (tPBM) are based allow for deep tissue penetration; exposure of subcortical and cortical structures to LLLT interventions is associated with increased perfusion, cellular oxygenation, and renormalization of functional electrophysiological networks [12].

Despite differences in the clinicopathogenesis of neurodegenerative disorders, tPBM is thought to directly influence mitochondrial dysfunction and oxidative inflammatory processes [13, 14]. Neuropathophysiological correlates of Alzheimer's dementia (AD) include, but are not limited to, neurofibrillary tangles; dystrophic neuritis; amyloid precursor protein deposits and increased phosphorylated tau concentrations [13–16]. The inability for β-amyloid concentrations to be adequately decreased results in the breakdown of microtubular assemblies due to hyperphosphorylated tau. Hyperphosphorylation is a biological process that mediates the regulation of mitosis. Because hyperphosphorylation is a signaling process that regulates cell division, abnormalities in microtubules can cause toxicity to cells. Disruptions of the polymerization dynamics of microtubules can result in synaptic failure as these cells are implicated in maintenance of cell structure and homeostatic regulation of cellular metabolic demand [13–16].
