**6. Tau-based therapeutics strategies**

So far, the US Food and Drug Administration (FDA) has granted seven prescription drugs for the treatment of AD. Three of these drugs, Donepezil (Eisai Co., Ltd., Pfizer), Galantamine (Janssen, Ortho-McNeil Pharmaceutical, Sanochemia Pharmazeutika, Shire, Takeda Pharmaceutical Company) and Rivastigmine (Novartis Pharmaceuticals Corporation), are cholinesterase inhibitors that prevent the breakdown of acetylcholine in the brain. Rivastigmine has also been approved for the treatment of PD. Applications of Donepezil in the treatment of dementia with Lewy bodies, Down's syndrome and PD are under clinical trial. The forth drug Memantine (Forest Laboratories, Inc., H. Lundbeck, Merz Pharma) is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. The fifth drug Suvorexant (Merck), an orexin receptor antagonist, is approved for treating sleep disorders in AD. The sixth drug Tacrine is a reversible acetylcholinesterase inhibitor, but has been discontinued because of its hepatotoxicity (Pfizer, Shionogi Pharma). In 2021, Aduhelm (Aducanumab), a human IgG1 monoclonal antibody against Aβ (Biogen, Neurimmune), was approved as the first immunotherapy for AD. However, most therapies exhibit limited benefits and do not prevent or slow down the progression of the disease [122].

Based on the extensive understanding of AD pathogenesis, a large number of therapies targeting tau have been developed recently. To data, among the 137 active therapeutic clinical trials for AD, FTD and PSP, 17 targeted tau (https://www. alzforum.org/therapeutics).
