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  Indian J Med Microbiol
 

Figure 1: Developmental level of anti-Alzheimer drugs. Drugs available in clinical settings are in black letters, and the drugs not yet developed for clinical use are in red letters. Level 1 drugs were used to improve cerebral circulation and/ or cerebral metabolism until late 1990s. Most of these drugs, however, were abandoned in 1996 because no clinical benefits were confirmed by reevaluation. Level 2 drugs include those targeting neurotransmitters, hormones, and neurotrophic factors. Acetylcholine esterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA antagonist (memantine) are presently prescribed in most countries to treat patients with Alzheimer's disease. Level 3 drugs are monoclonal antibody therapeutics including aducanumab, lecanemab and others. Aducanumab was granted expedited approval by FDA in 2021. Level 4 drugs are not yet used in clinical settings. Drugs targeting amyloid (aiming for reduced production, reduced aggregation, and/ or increased clearance), paired helical filaments (PHF; reduced aggregation of tau, reduced protein kinases, increased phosphatases), and neuronal loss (anti-apoptosis, chaperone induction, anti-oxidase stress) are under development.

Figure 1: Developmental level of anti-Alzheimer drugs. Drugs available in clinical settings are in black letters, and the drugs not yet developed for clinical use are in red letters. Level 1 drugs were used to improve cerebral circulation and/ or cerebral metabolism until late 1990s. Most of these drugs, however, were abandoned in 1996 because no clinical benefits were confirmed by reevaluation. Level 2 drugs include those targeting neurotransmitters, hormones, and neurotrophic factors. Acetylcholine esterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA antagonist (memantine) are presently prescribed in most countries to treat patients with Alzheimer's disease. Level 3 drugs are monoclonal antibody therapeutics including aducanumab, lecanemab and others. Aducanumab was granted expedited approval by FDA in 2021. Level 4 drugs are not yet used in clinical settings. Drugs targeting amyloid (aiming for reduced production, reduced aggregation, and/ or increased clearance), paired helical filaments (PHF; reduced aggregation of tau, reduced protein kinases, increased phosphatases), and neuronal loss (anti-apoptosis, chaperone induction, anti-oxidase stress) are under development.