Alzheimer's disease (AD) is a major form of senile dementia, characterized by 
progressive memory and neuronal loss combined with cognitive impairment. AD is 
the most common neurodegenerative disease worldwide, affecting one-fifth of 
those aged over 85 years. Recent therapeutic approaches have been strongly 
influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, 
glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), 
formation of intraneuronal neurofibrillary tangles (NTFs), and 
neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD 
result in a progressive and significant loss of cognitive and behavioral 
function. Current AD medications, memantine and acetylcholinesterase inhibitors 
(AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, 
but they are not curative. Since 2003, no new drugs have been approved for the 
treatment of AD. This article focuses on the current research in clinical trials 
targeting the neuropathological findings of AD including acetylcholine response, 
glutamate transmission, Aβ clearance, tau protein deposits, and 
neuroinflammation. These investigations include acetylcholinesterase inhibitors, 
agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or 
γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau 
protein, as well as anti-inflammation compounds. Ongoing Phase III clinical 
trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, 
and aducanumab) seem to be promising. Using small molecules blocking 5-HT6 
serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and 
verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase 
III clinical trials. We here systemically review the findings from recent 
clinical trials to provide a comprehensive review of novel therapeutic compounds 
in the treatment and prevention of AD.