Table 2.

Anti-amyloid and tau antibodies have been developed and commonly failed at curing the disease in previous clinical trials

Drug	Type	Target	Result
Lecanemab	mAb	Aβ protofibrils	Phase III trial underway, slows progression22 Phase III trial underway, slows progression22
Donanemab	mAb	Established Aβ plaques	Shows signs of benefit in phase II trial23 Shows signs of benefit in phase II trial23
Crenezumab	mAb	Binds to Aβ oligomers and monomers	Stopped at Phase III trials, not likely to meet endpoints24,25
Aducanumab	mAb	Aggregated Aβ	Decrease Aβ and slow cognitive decline as of Phase II trials12,26,27
Bapineuzumab	mAb	Aggregated Aβ	Failed to decrease cognitive decline28 Failed to decrease cognitive decline28
Verubecestat	BACE1 Inhibitor	Enzyme cleavage of APP	Failed to decrease cognitive decline and had treatment-related adverse events in Phase III trials29,30
Atabecestat	BACE1 Inhibitor	Enzyme cleavage of APP	Dose-related cognitive worsening and neuropsychiatric adverse events (AEs) in Phase III trials31,32
CNP520	BACE1 Inhibitor	Enzyme cleavage of APP	Lack of efficacy and worsens cognition in Phase III trials33,34
Lanabecestat	BACE1 Inhibitor	Enzyme cleavage of APP	Lack of efficacy and did not slow cognitive decline in Phase III trials35 Lack of efficacy and did not slow cognitive decline in Phase III trials35
Solanezumab	mAb	Aggregated Aβ	Failed to decrease cognitive decline in Phase III trials36,37
Gantenerumab	mAb	Aggregated Aβ	Failed to decrease cognitive decline38,39
Ponezumab	mAb	Aggregated Aβ	Abandoned after phase II trials40,41
Tideglusib	(GSK-3β) protein kinase inhibitor	Phosphorylated tau	No significant clinical benefit in phase II trials42
trx0014 and lmtm	Methylene blue dye derivative	Inhibit tau aggregation	Technique and efficacy in slowing cognitive decline are controversial43,44
AN1792	Vaccine	Anti-Aβ	Discontinued, 6% of participants developed meningoencephalitis, with no significance in Aβ antibody development45,46,47
UB-311	Vaccine	Anti-Aβ	Latest clinical trial drug in Phase II, shown to be well-tolerated but safety profile like placebo48

Here, we describe some of the most reported therapeutics targeting AD, their drug classification, specific target in the Alzheimer’s pathway, and a summarized result of the human clinical trial. Most of the drugs tested in clinical trials have been immunotherapy-based monoclonal antibodies (mAb) targeting one singular protein, primarily amyloid: with a failure rate of these drugs near 100%.