Table 6. Drugs under clinical trial for AD treatment.

Drug name	Structure	Mode of action	Class	National Clinical Trial number
Phase I
Disease-modifying biologicals
	Mode of action
MK-2214	Anti-tau monoclonal antibody		Tau	NCT05466422
SHR-1707	Prevent Aβ plaque and activate microglia to phagocytize various forms of Aβ		Amyloid	NCT06199037
NIO752	Antisense oligonucleotide to tau, decreasing the abundance of tau aggregates at neuromuscular junction		Tau	NCT06372821
IBC-Ab002	Humanized IgG1 antibody inhibits an immune checkpoint protein (PD-L1), stimulating the immune system		Inflammation/immunity	NCT05551741
ALN-APP	Small interfering RNA targeting the amyloid precursor protein mRNA		Amyloid	NCT05231785
CpG1018	Immune adjuvant made up of short, unmethylated cytosine–phosphate–guanine oligodeoxynucleotides, stimulate clearance of amyloid pathology		Inflammation/immunity	NCT05606341
AL003	Monoclonal antibody (MAb) targeting SIGLEC-3 (CD33), reactivates microglia and immune cells in the brain, improves microglial clearance of toxic proteins		Inflammation	NCT03822208
AAV-hTERT	Extending telomeres may benefit AD, reduce Aβ-induced neurotoxicity, and effects on multiple cellular pathways		Epigenetic	NCT04133454
Lu AF87908	MAb to reduce tau		Tau	NCT04149860
LY3372993	MAb to reduce amyloid (N3pG-AB)		Amyloid	NCT06653153
AAVrh.10hAPOE2	MAb targeting SIGLEC-3 (CD33), reactivates microglia and immune cells in the brain, improves microglial clearance of toxic proteins		Epigenetic	NCT05400330
XPro1595	TNF inhibitor, reduces neuroinflammation		Inflammation	NCT05318976
GSK933776	MAb against N-terminus of Aβ		Amyloid	NCT00459550
ALZ-101	Vaccine against soluble Aβ oligomers		Amyloid	NCT05328115
VT301	Regulatory T-cells (Tregs)		Inflammation	NCT05016427
CAD106	CAD106 combines multiple copies of Aβ1-6 peptide derived from the N-terminal B cell epitope of Aβ, coupled to a Qβ virus-like particle. In animals, CAD106 induced Aβ-antibody titers without activating Aβ-reactive T cells		Amyloid	NCT01097096
KHK6640	MAb that consists of anti-Aβ-peptide		Amyloid	NCT02377713
NPT088	An Ig-fusion general amyloid interaction motif (GAIM) based dimer		Amyloid	NCT03008161
Disease-modifying drugs
BDPP (2S,4S)-(−)-2,4-bis(diphenylphosphino)pentane		Prevents Aβ and tau aggregation	Proteostasis/proteinopathies	NCT02502253
BEY2153	Aβ and tau aggregation inhibitor, inhibits neuronal death		Proteostasis/proteinopathies	NCT04476303
Dabigatran		Direct thrombin inhibitor, reduce neurovascular damage	Vasculature	NCT03752294
Dexmedetomidine		Selective α2-adrenergic receptor agonist, neuroprotection	Circadian rhythm	NCT06052254
Edicotinib		CSF-1R antagonist, attenuates microglial proliferation and neurodegeneration	Inflammation	NCT04121208
Efavirenz		NNRTI, promotes cholesterol removal, enhances amyloid reduction	Epigenetics	NCT03706885
Emtricitabine		NRTI, reduces neuroinflammation	Inflammation	NCT04500847
MK-4334		Positive allosteric modulators of α7 nAChR	Growth factors and hormones	NCT03740178
NNI-3624-(3-cyano-6,7-dimethylquinolin-2-yl)-N-(2-ethoxyphenyl)-1,4-diazepane-1-carbothioamide		Enhance neurogenesis, activates progenitor cells	Neurogenesis	NCT04074837
REM0046127	Regulates calcium dyshomeostasis, tau and Aβ reduction		Synaptic plasticity/neuroprotection	NCT04672135
Salsalate		NSAID to reduce inflammation	Inflammation	NCT03277573
TC-5619 N-((2S,3R)-2-(pyridin-3-ylmethyl)quinuclidin-3-yl)benzofuran-2-carboxamide		Partial agonist at the α7 subtype of the neural nicotinic acetylcholine receptors	Cognition enhancement	NCT01254448
TPI-287 (1S,4S,7S,7aR,7a1S,10aS,11aR,13aS,13bR)-1-(benzoyloxy)-4-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-5-methylhexanoyl)oxy)-2-hydroxy-5,7a1,14,14-tetramethyl-9-vinyl-1,3,4,7,7a,7a1,10a,11,11a,13b-decahydro-2H-8,10,12-trioxa-2,6-methanocyclobuta[b]cyclodeca[de]naphthalene-7,13a(13H)-diyl diacetate		Stabilization of microtubule	Tau	NCT01966666
CMS121 4-(4-(cyclopentyloxy)quinolin-2-yl)benzene-1,2-diol		Fatty acid synthase inhibitor it protects against excess lipid peroxidation and inflammation and alleviates cognition	Inflammation	NCT05318040
Oxaloacetate		Improves mitochondrial function	Bioenergetics	NCT02593318
Telmisartan		Angiotensin II receptor blocker	Vasculature	NCT02471833
Trehalose		Induces autophagy and promotes clearance of aggregated proteins	Cell death	NCT05332678
Vorinostat		Histone deacetylase (HDAC) inhibitor, enhanced synaptic plasticity	Epigenetics	NCT03056495
Symptom-reducing small molecules
MK-1942	Improves mitochondrial structure and function		Neurotransmitter receptors	NCT04308304
MK-8189	Phosphodiesterase 10A inhibitor		Behavioural changes	NCT05227118
Memogain		AChE/BuChE MTDL	Neurotransmitter receptors	—
Phase II
Disease-modifying biologicals
AL002	MAb targeting TREM2 receptors to promote microglial clearance of Aβ		Inflammation	NCT05744401
ACI-35	Active immunotherapy targeting tau		Tau	NCT04445831
ABvac40	Active immunotherapy to remove Aβ		Amyloid	NCT03461276
AADvac1	This is an active vaccine designed to elicit an immune response against pathologically modified forms of tau protein		Tau	NCT01850238
BCG vaccine	Vaccination against tuberculosis infection, immunomodulator		Inflammation	NCT05004688
Bryostatin 1	Protein kinase C inhibitor, facilitates synaptogenesis		Synaptic plasticity/neuroprotection	NCT04538066
Daratumumab	MAb targeting CD38, regulates microglial activity		Inflammation/immunity	NCT04070378
Etanercept	Inhibits the function of a pro-inflammatory cytokine called tumor necrosis factor alpha (TNF-α)		Inflammation	NCT01068353
Crenezumab	MAb targeting soluble Aβ oligomers		Amyloid	NCT01723826
Gosuranemab	MAb targeting truncated form of tau		Tau	NCT03352557
Gantenerumab	Human IgG1 Ab against Aβ fibrils		Amyloid	NCT01760005
Pepinemab	MAb directed at semaphorin 4D to reduce inflammation		Inflammation	NCT04381468
GV1001	hTERT peptide vaccine, mimics extra-telomeric functions to inhibit neurotoxicity, apoptosis, and reactive oxygen species		Epigenetic	NCT05303701
GB301	Regulatory T cells, reduce neuroinflammation		Inflammation/immunity	NCT04468659
IVIG	Polyclonal antibody, remove amyloid		Amyloid	NCT01300728
JNJ-63733657	MAb targeting soluble tau		Tau	NCT04619420
IONIS MAPTRx	Antisense oligonucleotide targeting tau expression, MAPT RNA inhibitor		Tau	NCT03186989
R07126209	Anti-Aβ MAb with enhanced BBB penetration		Amyloid	NCT04639050
Semorinemab	MAb to remove extracellular tau		Tau	NCT03828747
Tilavonemab	MAb to remove tau and prevent propagation		Tau	NCT02880956
Zagotenemab	MAb to remove tau and reduce tau propagation		Tau	NCT03518073
Disease-modifying drugs
Allopregnanolone		GABA-A receptor modulator, promote neurogenesis and reduce inflammation	Growth factors/hormones	NCT04838301
Telmisartan + perindopril		Telmisartan: angiotensin II receptor blocker	Vasculature	NCT02085265
		Perindopril: angiotensin converting enzyme inhibitor
Empagliflozin		SGLT2 inhibitor, improve glycemic control, enhance neuronal function	Metabolism and bioenergetics	NCT05081219
Sodium phenylbutyrate + tauroursodeoxycholic acid		Reduce cell death associated with mitochondrial dysfunction, modulate neuroinflammation	Cell death	NCT03533257
Fosgonimeton		Activates signalling via the hepatocyte growth factor system to regenerate neurons and enhance synaptic plasticity	Synaptic plasticity/neuroprotection	NCT04488419
AR1001	PDE-5 inhibitor it improves synaptic plasticity		Synaptic plasticity/neuroprotection	NCT05531526
Blarcamesine		Sigma-1 receptor agonist, M2 antagonist, ameliorate oxidative stress, protein misfolding, mitochondrial dysfunction and inflammation	Synaptic plasticity/neuroprotection	NCT04314934
Zatolmilast		PDE-4 inhibitor, prolongs cAMP activity and improves neuronal plasticity	Synaptic plasticity/neuroprotection	NCT03817684
Benfotiamine		Synthetic thiamine to improve neuronal function	Metabolism and bioenergetics	NCT06223360
Bromocriptine		Dopamine agonist with anti-Aβ effects	Neurotransmitter receptors	NCT04413344
DHA (docosahexanoic acid)		Omega 3 fatty acid, improve synaptic function, antioxidant	Oxidative stress	NCT00440050
Dapagliflozin		SGLT2 inhibitor, to improve insulin sensitivity and CNS glucose metabolism	Metabolism and bioenergetics	NCT03801642
Elayta		Sigma-2 receptor antagonist, competes with oligomeric Aβ binding, protect against Aβ-induced synaptic toxicity	Synaptic plasticity/neuroprotection	NCT05531656
Edonerpic acid		Neurotrophic agent, activates sigma receptors to preserve synaptic plasticity, protect against Aβ toxicity	Synaptic plasticity/neuroprotection	NCT00663936
Dasatinib + quercetin		Dasatinib: tyrosine kinase inhibitor	Inflammation/immunity	NCT05422885
		Quercetin: flavonoid, senolytic therapy approach to reduce senescent cells and tau aggregation
Lamivudine		Nucleoside reverse transcriptase inhibitor, reduces genetic rearrangements	Epigenetic	NCT04552795
l-Serine		Dietary amino acid, reduce brain inflammation and preserve nerve cells	Inflammation	NCT05331144
Liraglutide		Glucagon-like peptide 1 receptor agonist, improve CNS glucose metabolism	Metabolism and bioenergetics	NCT01469351
Lupron		GnRH receptor agonist, reduce effects of elevated GnRH and gonadotropins on the brain	Growth factors and hormones	NCT00063310
Montelukast		Cysteinyl leukotriene type 1 (cysLT-1) receptor antagonist, effects on inflammatory processes, neuronal injury, blood–brain-barrier integrity, and Aβ protein accumulation	Inflammation	NCT03991988
Nilotinib		Tyrosine kinase inhibitor, autophagy enhancer, promotes clearance of Aβ and tau	Proteostasis/proteinopathies	NCT05143528
Neflamapimod		p38 MAPK-α inhibitor, enhance endolysosomal function to reduce synaptic dysfunction	Synaptic plasticity/neuroprotection	NCT03402659
Nicotinamide		HDAC inhibitor, reduce tau-induced microtubule depolymerization and tau phosphorylation	Tau	NCT00580931
Tacrolimus		Calcineurin inhibitor, prevent Aβ-induced dendritic spine loss and synaptic dysfunction	Synaptic plasticity/neuroprotection	NCT04263519
PU-AD8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine		Heat shock protein 90 inhibitor, prevent aggregation and hyperphosphorylation of tau	Tau	NCT03935568
PF-044479436-((3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one		Selective phosphodiesterase 9 (PDE9) inhibitor	Cognition enhancement	NCT00988598
Perindopril		Angiotensin converting enzyme inhibitor	Vasculature	NCT02085265
PQ912(S)-1-(1H-benzo[d]imidazol-6-yl)-5-(4-propoxyphenyl)imidazolidin-2-one		Glutaminyl cyclase (QC) enzyme inhibitor to reduce pyroglutamate Aβ (pGlu-Aβ) production	Amyloid	NCT02389413
Rapamycin		mTOR inhibitor, ameliorate metabolic and vascular effects of aging	Proteostasis/proteinopathies	NCT04629495
S-Equol		Agonist of non-hormonal estrogen receptor B located on mitochondria to potentiate mitochondrial function	Metabolism and bioenergetics	NCT03101085
Sovateltide		Endothelin B receptor agonist, augments activity of neuronal progenitor cells	Neurogenesis	NCT04052737
Vafidemstat		HDAC demethylase inhibitor and MAO-B inhibitor, neuroprotective	Synaptic plasticity/neuroprotection	NCT03867253
Valacyclovir		Antiviral against HSV-1 and -2 infection, prevent Aβ aggregation and plaque deposition	Infection/immunity	NCT03282916
Symptom-reducing small molecules
AD-35phosphenoperoxoic acid compound with 6′-(2-(1-(pyridin-2-ylmethyl)piperidin-4-yl)ethyl)spiro[cyclopropane-1,5′-[1,3]dioxolo[4,5-f]isoindol]-7′(6′H)-one		Acetylcholinesterase inhibitor	Neurotransmitter receptors	NCT03625401
Huperzine A		NMDA receptor antagonist and AChE inhibitor (MTDL)	Neurotransmitter receptors	NCT00083590
Dexmedetomidine		Sublingual dexmedetomidine, selective α2-adrenergic receptor agonist	Neurotransmitter receptors	NCT06052254
CORT108297(R)-4a-(ethoxymethyl)-1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline		Selective glucocorticoid receptor antagonist, reduce neuroendocrine stress responses	Hormone (cognition enhancement)	NCT04601038
Dronabinol		CB1 and CB2 endocannabinoid receptor partial agonist	Neurotransmitter receptors	NCT02792257
Nicotine		Nicotinic acetylcholine receptor agonist enhances cognition	Neurotransmitter receptors	NCT02720445
Prazosin		α-1 adrenoreceptor antagonist	Neurotransmitter receptors	NCT01126099
SAGE-718	First-in-class, oxysterol-based positive allosteric modulator (PAM) of N-methyl-d-aspartate (NMDA) receptors		Neurotransmitter receptors	NCT05619692
Phase III
Disease-modifying biologicals
Donanemab	MAb specific for pyroglutamate form of Aβ		Amyloid	NCT06566170
Gantenerumab	MAb directed at Aβ plaques and oligomers		Aβ	NCT01760005
Lecanemab	MAb directed at Aβ protofibrils		Aβ	NCT05269394
UB311	Vaccine that stimulates a T-helper type 2 regulatory immune response over a T-helper type 1 pro-inflammatory response, and to avoid cross-reactivity with similar endogenous antigens, i.e., autoimmune responses		Amyloid	NCT02551809
Disease-modifying drugs
Atuzaginstat		It reduces neuroinflammation and hippocampal degeneration	Inflammation/infection due to P. gingivalis	NCT03823404
Blarcamesine		Sigma-1 receptor agonist, M2 autoreceptor antagonist. It ameliorates oxidative stress, protein misfolding, mitochondrial dysfunction, and inflammation	Synaptic plasticity	NCT04314934
GV-971sodium (2S,3S,4S,5S,6R)-6-((1-carboxylato-2,4-dihydroxyhexan-3-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate oxo-l3-methanolate		Algae-derived acidic oligosaccharides, changes microbiome to reduce peripheral and central inflammation	Inflammation	NCT04520412
Icosapent ethyl		Purified form of the omega-3 fatty acid EPA. It improves synaptic function and reduces inflammation	Oxidative stress	NCT02719327
Losartan + amlodipine + atorvastatin		Losartan: angiotensin II receptor blocker	Vasculature	NCT02913664
		Amlodipine: calcium channel blocker
		Atorvastatin: anti-hyperlipidemic (HMG-CoA reductase inhibitor)
Metformin		Insulin sensitizer to improve CNS glucose metabolism	Metabolism and bioenergetics	NCT04098666
Omega-3 fatty acids		Antioxidant	Oxidative stress	NCT01058941
NE3107		MAPK-1/3 inhibitor. It reduces pro-inflammatory NFκB activation	Inflammation	NCT04669028
Tricaprilin		Caprylic triglyceride. It induces ketosis and improves mitochondrial and neuronal function	Metabolism and bioenergetics	NCT05809908
Troriluzole		Glutamate modulator; prodrug of riluzole. It improves synaptic function	Synaptic plasticity/neuroprotection	NCT03605667
Leuco-methylthioninium (LMTX) mesylate		Tau protein aggregation inhibitor	Tau	NCT03539380
Symptom-reducing small molecules
Brexpiprazole		Atypical antipsychotic, D2 receptor partial agonist	Neurotransmitter receptors	NCT03548584
Dextromethorphan + quinidine		Sigma1 receptor agonist, NMDA receptor antagonist	Neurotransmitter receptors	NCT01584440
Donepezil + memantine		Donepezil: binds to AChE and reversibly inactivates it	Cognition enhancement	NCT02580305
		Memantine: blocks current flow through NMDA receptor channels
Caffeine		Pleiotropic effect on CNS	Metabolism and bioenergetic, cognition enhancement	NCT00692510
Escitalopram		Selective serotonin reuptake inhibitor	Neurotransmitter receptors	NCT05004987
Guanfacine		α-2 adrenergic agonist	Cognition enhancement	NCT03116126
Mirtazapine		α-1 antagonist	Neurotransmitter receptors	NCT01505504
Nabilone		Synthetic cannabinoid, CB1 and CB2 receptor agonist. It suppresses neuronal excitability and neurotransmitter release	Neurotransmitter receptors	NCT04516057
Octohydroamino-acridine succinate		AChE inhibitor	Cognition enhancement	NCT01569516