In the context of peroxynitrite formation, these findings make perfect sense. Peroxynitrites are likely the most important oxidant in Alzheimer's disease. Peroxynitrite-mediated nitration is critical to the aggregation of amyloid plaques and therefore their formation precedes the aggregation of amyloid plaques (similarly peroxynitrite-mediated nitration prevents the degradation of hyperphosphorylated tau proteins and precedes the formation of neurofibrillary tangles). Peroxynitrites also mediate the nitration of NMDA receptors which results in the efflux of glutamate which causes inflammation and the influx of calcium which causes the death of neurons. In Alzheimer's patients with continued high levels of protein kinase C activity, high levels of peroxynitrites by lowering serotonin, aceytlcholine levels, and blood flow in the brain can also contribute to neuropsychiatric problems.

Peroxynitrites inhibit the transport of choline and the enzyme that produces acetylcholine (choline acetyltransferase). It also oxidizes g protein-coupled receptors involved in short-term memory (muscarinic acetylcholine), mood
(serotonin), sleep (melatonin), social recognition (oxytocin), smell (olfactory), alertness (dopamine), and brain growth (adrenergic). Nearly all of the damage in Alzheimer's disease can be explained by peroxynitrite caused or mediated oxidation and nitration.

Peroxynitrite scavengers have reversed Alzheimer's disease in vitro, in animals,and in human beings. The most effective peroxynitrites scavangers are methoxyphenols. These include eugenol in rosemary essential oil (and in other essential oils such as clove, cinnamon leaf, and bay laurel)and ferulic acid, vanillic acid, and syringic acid in heat-processed ginseng. Rosemary essential oil and lemon essential oil (which contains the methoxyphenol geraniol) given in the morning and lavender and orange in the evening (to try to offset the potential agitation caused by the stimulating essential oils) led to significant improvements in cognitive function related to personal orientation in people with dementia and especially with Alzheimer's disease (Jimbo, et al. Effect of aromatherapy on patients with Alzheimer's disease). Heat-processed ginseng improved both cognitive and non-cognitive function in people with moderately severe Alzheimer's disease (including improvements in behavior because ferulic acid may lower protein kinase C activity; glucuronolactones is another peroxynitrite scavenger that may have a similar effect in Alzheimer's disease; Heo, Heat-processed ginseng enhances cognitive function in patients with moderately severe Alzheimer's disease).

The methoxy group in methoxyphenols donate two electrons and make the extraction of hydrogen atoms easier. The donation of hydrogen atoms partially restores function to g protein-coupled receptors involved in short-term memory, mood, sleep, social recognition, smell, alertness, and brain growth. They readily scavenge peroxynitrites: ONOO- + 2e- + 2H+= H20 + NO2-. Moreover, water may be critical to the de-nitration of tyrosine that is involved in the aggregation of amyloid plaques, that prevents the degradation of hyperphosphorylated tau proteins (neurofibrilllary tangles), and in the activation of NMDA receptors which results in the efflux of glutamate and the influx of calcium: Tyrosine-NO2 + H20= Tyrosine-H + H+ + NO3-. Potentialy, then, most of the deficits caused by Alzheimer's disease can be reversed by the more effective peroxynitrites scavengers if they reach the brain in large enough concentrations.