Alzheimers Dement. 2026 Apr;22(4):e71381. doi: 10.1002/alz.71381.
ABSTRACT
INTRODUCTION: S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple neuronal pathways, including tau dephosphorylation. Reduced SAMe availability has been reported in the Alzheimer’s disease (AD) brain, prompting interest in supplementation as a potential therapeutic strategy.
METHODS: This multicenter, randomized, double-blind, placebo-controlled phase 2 study recruited people (n = 63) with a clinical AD diagnosis. Participants received 180 days of SAMe (400 mg daily) or placebo. Primary outcome was change in plasma phosphorylated tau (p-tau)217 concentration. Secondary endpoints included safety, tolerability, and cognitive outcomes.
RESULTS: Mean percentage change in plasma p-tau217 in the SAMe group was an increase of 53.22 (standard deviation [SD] 159.19) compared to 25.34 (SD 94.83) in the placebo group (standardized mean difference 37.58, 95% confidence interval -32.61, 107.76; p = 0.288). No significant differences were observed in safety or other secondary endpoints.
DISCUSSION: SAMe did not demonstrate disease-modifying efficacy at the dose and duration studied; however it was safe and well tolerated.
TRIAL REGISTRATION: ACTRN12620000506998. Registered on the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au).
PMID:41980907 | DOI:10.1002/alz.71381
