No apparent effect of naproxen on CSF markers of innate immune activation

Ann Clin Transl Neurol. 2019 Jun 6;6(6):1127-1133. doi: 10.1002/acn3.788. eCollection 2019 Jun.


We studied 78 participants having a parental or multiple-sibling history of Alzheimer's disease (AD) in a two-year randomized placebo-controlled trial of naproxen 220 mg b.i.d. for mitigation of early AD pathogenesis. Naproxen was detected in cerebrospinal fluid at concentrations ~100 times lower than in plasma, but produced negligible change in immune markers. The repeated lack of benefit in AD prevention trials using naproxen and related drugs may reflect limited CNS permeability, lack of expected drug effects, or both. These findings suggest reconsideration of implications from results of AD prevention trials using anti-inflammatory drugs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / drug therapy
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / cerebrospinal fluid*
  • Celecoxib / therapeutic use
  • Cytokines / cerebrospinal fluid
  • Female
  • Humans
  • Interferon alpha-2 / cerebrospinal fluid
  • Interleukin 1 Receptor Antagonist Protein / cerebrospinal fluid
  • Male
  • Middle Aged
  • Naproxen / cerebrospinal fluid*
  • Naproxen / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cytokines
  • IL1RN protein, human
  • Interferon alpha-2
  • Interleukin 1 Receptor Antagonist Protein
  • Naproxen
  • Celecoxib

Grant support

This work was funded by McGill University grant ; Canada Fund for Innovation grant ; Government of Canada grant ; Fonds de Recherche du Québec‐Santé grant ; J.L. Levesque Foundation grant ; Douglas Mental Health University Institute Foundation grant .