Table 2.

Anti-AD drugs with anti-ageing properties in trials

Candidate drugs	Relevant AD hallmark of target	Mechanism of action	Outcome	Current clinical trial
Lecanemab	Loss of proteostasis	Monoclonal antibody directed at Aβ plaques and oligomers	Reduces Aβ deposition	Phase 3 (NCT03887455)
Aducanumab	Loss of proteostasis	Monoclonal antibody directed at Aβ plaques and oligomers	Reduces Aβ deposition and controls inflammation	Phase 3 (NCT04241068)
Donanemab	Loss of proteostasis	Monoclonal antibody specific for the pyroglutamate form of Aβ	Reduces Aβ deposition	Phase 3 (NCT04437511)
Donanemab & Aducanumab	Loss of proteostasis	Combination of two monoclonal antibodies	Reduces Aβ deposition	Phase 3 (NCT05108922)
Simufilam (PTI-125)	Loss of proteostasis	Filamin A protein inhibitor	Stabilizes the interaction between amyloid-alpha-7 and nicotinic receptor	Phase 3 (NCT04994483)
Gantenerumab	Loss of proteostasis	Monoclonal antibody directed at Aβ plaques and oligomers	Reduces Aβ deposition	Phase 3 (NCT03444870)
TRx0237	Loss of proteostasis	Inhibitor of tau protein aggregation	Reduces tau protein aggregation	Phase 3 (NCT04770220)
Valiltramiprosate (ALZ-801)	Loss of proteostasis	Prodrug of tramiprosate	Inhibits the aggregation of Aβ into toxic oligomers	Phase 3 (NCT04770220)
ACI-35	Loss of proteostasis	Active immunotherapy targeting tau	Reduces tau protein aggregation	Phase 2 (NCT04445831)
Nilotinib BE	Disabled macroautophagy	Tyrosine kinase inhibitor; autophagy enhancer	Increases clearance of Aβ and tau	Phase 3 (NCT05143528)
Losartan and Amlodipine and Atorvastatin + exercise	Deregulated nutrient sensing	Angiotensin II receptor blocker (losartan), calcium channel blocker (amlodipine) and cholesterol agent (atorvastatin)	Regulates vascular energy metabolism	Phase 3 (NCT02913664)
Metformin	Deregulated nutrient sensing	Insulin sensitizer	Improves glucose metabolism in the CNS	Phase 3 (NCT04098666)
Semaglutide	Deregulated nutrient sensing	GLP-1 agonist	Reduces neuroinflammation and improves insulin signalling in the brain	Phase 3 (NCT04777396)
Tricaprilin	Mitochondrial dysfunction	Caprylic triglyceride	Induces ketosis and improves mitochondrial and neuronal function	Phase 3 (NCT03446001)
MitoQ	Mitochondrial dysfunction	Mitochondria‐targeting antioxidant	Reduces systemic oxidative stress and increases cerebral oxygenation	Phase 1 (NCT03514875)
AGB101 (low-dose levetiracetam)	Cellular senescence	Synaptic plasticity/neuroprotection	Reduces Aβ-induced neuronal overactivity	Phase 3 (NCT03486938)
Atuzaginstat (COR388)	Cellular senescence	Synaptic plasticity/neuroprotection	Reduces Aβ-induced neuronal overactivity	Phase 3 (NCT03823404)
Dasatinib +  Quercetin	Cellular senescence	Tyrosine kinase inhibitor (dasatinib) and flavonoid (quercetin)	Decreases the number of senescent cells and tau aggregation	Phase 1 (NCT04063124 and NCT04785300) Phase 2 (NCT04685590)
Deferiprone	Cellular senescence	Iron-chelating agent	Reduces the amount of reactive oxygen species	Phase 2 (NCT03234686)
AVP-786	Altered intercellular communication	Sigma 1 receptor agonist and NMDA receptor antagonist	Controls neuropsychiatric symptoms	Phase 3 (NCT03393520)
AXS-05	Altered intercellular communication	NMDA receptor antagonist	Controls neuropsychiatric symptoms	Phase 3 (NCT04797715)
Donepezil	Altered intercellular communication	Acetylcholinesterase inhibitor	Improves cognitive impairment	Phase 3 (NCT04661280)
Caffeine	Altered intercellular communication	Adenosine antagonist; non-specific phosphodiesterase inhibitor	Improves cognitive impairment	Phase 3 (NCT04570085)
Blarcamesine (ANAVEX2-73)	Chronic inflammation	M2 autoreceptor antagonist	Improves oxidative stress, protein misfolding, mitochondrial dysfunction and inflammation	Phase 3 (NCT03790709)
Hydralazine	Chronic inflammation	Free radical scavenger	Controls inflammatory response caused by oxidative stress	Phase 3 (NCT04842552)
Icosapent ethyl (IPE)	Chronic inflammation	Purified form of the omega-3 fatty acid EPA	Improves synaptic function and reduces inflammation	Phase 3 (NCT02719327)
NE3107	Chronic inflammation	MAPK-1/3 inhibitor	Reduces activation of proinflammatory NFκB	Phase 3 (NCT04669028)
Canakinumab	Chronic inflammation	Anti-IL-1β monoclonal antibody	Reduces neuroinflammation	Phase 2 (NCT05189106)
Baricitinib	Chronic inflammation	Janus kinase inhibitor	Reduces neuroinflammation	Phase 2 (NCT05189106)
GV-971	Dysbiosis	Algae-derived acidic oligosaccharides	Regulates bacterial imbalance and reduces peripheral and central inflammation	Phase 3 (NCT04520412)