TNF and Alzheimer disease: In the context of betaine, another methyl-donor, human studies showed that betaine supplementation in AD patients results in: decreased levels of homocysteine, phosphorylated tau, and amyloid beta accumulation; a reduction in blood inflammatory markers such as interleukin-1 beta (IL-1β) and tumor necrotic factor-alpha (TNF-α); an increase in the levels of memory-related proteins such as NR1, NR2A, and NR2B (NMDA receptors); an increase in the levels of synaptic proteins such as synaptophysin, synaptotagmin, and phosphorylated synapsin I [146].