Table 1 Peer-reviewed clinical trials associated with positive Alzheimer’s disease outcomes following treatment with antimicrobials
Antimicrobial(s) | On-target effect(s) | Off-target effect(s) on AD-associated processes | Clinical trial: Study population | Clinical trial: Treatment dosage | Clinical trial: Improved AD outcomes |
|---|---|---|---|---|---|
Cycloserine | Broad-spectrum antibiotic [18] | Inhibits: PI3K/Akt pathway NO production Phosphorylation of LPS-induced ERK [19] | Probable AD patients (n = 91) Placebo-controlled Double-blind [20] | 5, 15, or 50 mg 2 × daily (oral) 10-week duration [20] | Implicit memory performance of words repeated across trials [20] |
AD patients (n = 17) Placebo-controlled Double-blind [21] | 50 or 100 mg 1 × daily 4-week duration [21] | ADAS-cog scores [21] | |||
Doxycycline and Rifampin | Enhances: PACAP receptors (Doxycycline) [24] Inhibits: Microglial inflammation (Rifampin) [25] | Probable AD and mild-to-moderate dementia patients (n = 101) Placebo-controlled Triple-blind [26] | 200 and 300 mg (Doxycycline and Rifampin, respectively) 1 × daily (oral) 3-month duration [26] | Functional behavior at 3 months ADAS-cog score at 6 months [26] | |
Helicobacter pylori eradication regimen: Omeprazole, clarithromycin, and amoxicillin | Proton-pump inhibitor (Omeprazole) [27] Macrolide antibiotic (clarithromycin) [28] Broad-spectrum antibiotic (amoxicillin) [29] | Inhibits: TGF- β upregulation in vivo (amoxicillin) [30] | H. pylori-positive patients with AD (n = 56) Placebo-controlled Triple-blind [31] | In accordance to clinical standard practice in Europe > 2-year follow-up period [31] | MMSE CAMCOG FRSSD [31] |
Antiherpetic treatment: Either acyclovir, famciclovir, ganciclovir, idoxuridine, penciclovir, tromantadine, valacyclovir, or valganciclovir | Antiviral [20] | Herpes simplex virus type 1 and/or type 2 patients (n = 8362, ≥ 50 years old) Placebo-controlled Triple-blind [32] | Self-administered, as needed Until onset of dementia > 10-year follow-up period [32] | Lower incidence of overall dementia (AD, vascular and other dementia) [32] | |
Sodium oligomannate (GV-971) | Inhibits Aβ fibrillization [33] | Inhibits: Gut dysbiosis Peripheral immune cells infiltration into the brain Neuroinflammation in animal models [33] | Probable AD patients (n = 818) Placebo-controlled Double-blind [34] | 2 × daily (oral) 36-week duration [34] | ADAS-cog12 scores [34] |
N-acetyl-L-cysteine (NAC) | Thiol antioxidant [35] Ameliorates psychiatric and neurological disorder-associated physiological processes [36, 37] | Broad-spectrum antibiotic | Probable AD patients (n = 43) Placebo-controlled Double-blind [41] | 50 mg/Kg/day ≤ 6-month duration [41] | Letter fluency task Wechsler Memory Scale [41] |
Moderate to late-stage AD patients (n = 12) Placebo-controlled [42] | 600 mg of NAC 2 × daily (oral) ≤ 9-month duration [42] | Dementia Rating Scale scores [42] |