Melatonin for Alzheimer's Disease
Also known as: N-acetyl-5-methoxytryptamine
Melatonin decline is one of the earliest biomarker changes in Alzheimer's, preceding cognitive symptoms by years.
Mechanism of Action
Melatonin inhibits amyloid-beta aggregation by binding to the histidine-13 residue of Aβ. It activates α-secretase (non-amyloidogenic pathway), reduces tau hyperphosphorylation through GSK3β inhibition, and promotes glymphatic clearance during sleep.
General mechanism: Pineal hormone. Mitochondrial antioxidant, Nrf2 activator, NLRP3 inhibitor, circadian regulator, anti-amyloid, immunomodulator.
Current Evidence
Observational studies show AD patients have 50-80% reduced melatonin levels. Supplementation trials show improved sleep and reduced sundowning. Disease-modification trials in early AD planned.
Clinical Status: Established for AD-related sleep disorders. Disease-modification trials planned.
Safety Profile
Extremely safe even at high doses. Drowsiness. No addiction potential. May affect reproductive hormones at very high doses.
Key Research Questions
- Can early melatonin supplementation prevent or delay AD onset?
- Does melatonin enhance glymphatic Aβ clearance during sleep?