Current AD treatment. Medications currently administered to AD patients are aimed at alleviating certain symptoms and improving cognition, behaviour and everyday function. The nucleus basalis of Meynert, the origin of cortically-projecting cholinergic neurons, is highly involved in the early stages of AD pathology. AD is, in fact, associated with a decline in acetylcholine synthesis capacity and cholinesterase inhibitor drugs are the most administered drug in AD treatment, acting to increase levels of acetylcholine in the brain (Xxxxxx and Xxxxxxxx, 2007). Out of five total medications approved by the US Food and Drug Administration (FDA), four are cholinesterase inhibitors and the fifth is an N-methyl-D-aspartate (NMDA) receptor antagonist (Xxxxxxxxx, 2013). Tacrine was the first ever cholinesterase inhibitor to be approved for AD treatment but is nowadays very rarely administered due to risks of hepatotoxicity. Currently, the cholinesterase inhibitors Donepezil, Rivastigmine and Galantamine are most commonly used to treat symptoms in mild to moderate AD and are shown to be effective in improving memory, confidence, motivation and general daily living. Memantine is a commonly used NMDA receptor antagonist, acting to reduce excessive excitatory activity (Xxxxxxx and Xxxxxxx, 2012). It is used in more severe cases of AD, and is associated with improved cognitive testing and behaviour. AD behavioural symptoms are also often treated with neuropsychiatric medication including antidepressants, anxiolytic medications and neuroleptic drugs (Xxxxxxx and Xxxxxxx, 2012). Since all current treatments for AD only provide symptomatic benefit and do not modulate the actual course of the disease, current studies are looking for agents that decrease Aβ production and/or aggregation or increase Aβ clearance from the brain. More recently, because of a series of failures of Aβ-based compounds in clinical trials, tau has emerged as a therapeutic target. However, only one anti-tau treatment has made it into clinical phase III trials thus far. Additional tau-targeting therapies are still in development stages, including immunotherapies and inhibition of GSK-3β. Preliminary studies in humans with lithium have been fairly promising, but lithium administration is controversial and risky and therefore progress on this potential treatment has been slow (Macdonald et al., 2008). Similarly, treatment with the tau aggregate inhibitor, methylene blue, was encouraging but did not lead to major conclusions (Xx...
