Conventional Alzheimer’s disease treatment relies heavily upon pharmacologic modulation of cholinergic and glutamatergic neurotransmission. This can result in symptomatic improvement, though the underlying progression of the disease is unaffected. Accumulation of amyloid beta and neurofibrillary tangles are challenging to target via pharmacologic means (Pangalos 2007).
Acetylcholinesterase inhibitors are typically first line pharmacotherapy for mild-to-moderate Alzheimer’s disease. They prevent the breakdown of acetylcholine, a chemical neurotransmitter in the brain, by inhibiting the enzyme acetylcholinesterase.
Tacrine, the first centrally-acting cholinesterase inhibitor approved by FDA for the treatment of Alzheimer's disease, was withdrawn from the U.S. market, due to possible liver toxicity (FDA 2013; Meng 2007; Mehta 2012). Cholinesterase inhibitors currently used in AD include donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) (Uzun 2011). Although studies have repeatedly found that acetylcholinesterase inhibitors may reduce Alzheimer’s symptoms, they do not halt or reverse the underlying disease process (Gauthier 2009; Hansen 2008).
NMDA Receptor Blockers
Memantine (e.g., Namenda®), an N-methyl-D-aspartate (NMDA) receptor antagonist (blocker), has been approved by the FDA for moderate to severe Alzheimer’s disease (Lo 2011). Although memantine may help decrease formation of NFTs, NMDA receptor antagonists have also been linked to serious adverse effects, which appear to be worsened in combination with acetylcholinesterase inhibitors (Creeley 2008).