Supplementary Material for: Modeling the Effects of Yoga on the Progression of Alzheimer’s Disease in a Dish

Alzheimer’s disease (AD) accounts for 80% of all dementia cases, making it the most common form of dementia. Aging serves as the main risk factor for AD, but early onset AD can also occur in individuals younger than 65 years. AD results from progressive neurodegeneration leading to dysfunctional synaptic transmission in the brain. The cascade hypothesis of AD states that amyloid precursor protein (APP) metabolism becomes impaired either by mutation or an interleukin-mediated stress response to injury, resulting in the splicing of harmful oligomeric forms of amyloid beta (Aβ). These oligomers disrupt extracellular receptor binding, intracellular function, and cellular membrane integrity. Yoga and meditative practices slow the progression of the cognitive decline associated with AD. However, the biological mechanisms underlying this therapeutic effect remain elusive. Here, we investigated the ability of neurotransmitters released during yoga and meditative practices to rescue neurons from synaptic dysfunction in an in vitro Alzheimer’s model created by culturing basal forebrain cholinergic neurons with physiologically relevant levels of the I-42 isoform of oligomeric Aβ (OΑβ_I-42). We found that the neurotransmitters dopamine and histamine produce a cooperative action with serotonin to reverse the loss of choline acetyltransferase (CHaT) by OΑβ_I-42. The loss of ChaT, the enzyme responsible for processing the cholinergic neurotransmitter acetylcholine, contributes to the synaptic dysfunction experienced during AD. These neurotransmitters inhibit nitric oxide synthesis caused by OΑβ_I-42, preventing oxidative and nitrosative stress. Serotonin activates an alternate cleavage of APP to produce a fragment with known neurotrophic effects, giving it the unique ability to inhibit the OΑβ_I-42 production cycle. We hypothesize here that these concerted actions lead to the protection of cholinergic synaptic transmission in AD.