A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease

J Alzheimers Dis. 2018;66(1):97-104. doi: 10.3233/JAD-180619.


Background: To date, the therapeutic paradigm for Alzheimer's disease (AD) has focused on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.

Objective: To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.

Methods: Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo.

Results: 474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.

Conclusion: Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD.

Keywords: Alzheimer’s disease; bioinformatics; biomarkers; clinical trial; inflammation; precision medicine; proteomics.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / epidemiology
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Double-Blind Method
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • Male
  • Precision Medicine / methods*


  • Anti-Inflammatory Agents, Non-Steroidal