Precision Medicine for Preventing Alzheimer’s Disease: Analysis of the ADAPT Study

Article type: Research Article

Authors: O’Bryant, Sid E.^{a; b; *} | Zhang, Fan^{a; b} | Johnson, Leigh A.^{a; c} | Hall, James^{a; b} | Petersen, Melissa^{a; b} | Oh, Esther S.^{d; e; f} | Lyketsos, Constantine G.^{e; f} | Rissman, Robert A.^{g; h}

Affiliations: [a] Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA | [b] Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA | [c] Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA | [d] Department of Medicine, Johns Hopkins School of Medicine, Baltimore, USA | [e] Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA | [f] Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA | [g] Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA | [h] VA San Diego Healthcare System, San Diego, CA, USA

Correspondence: [*] Correspondence to: Sid E. O’Bryant, PhD, University of North Texas Health Science Center, Institute for Translational Research, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA. Tel.: +1 817 735 2961; Fax: +1 817 735 0628; E-mail: [email protected].

Abstract: Background:The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) was the first-ever large-scale anti-inflammatory prevention trial targeting Alzheimer’s disease. Objective:The overall goal of this study was to evaluate predictive blood biomarker profiles that identified individuals most likely to be responders on NSAID treatment or placebo at 12 and 24 months. Methods:Baseline (n = 193) and 12-month (n = 562) plasma samples were assayed. The predictive biomarker profile was generated using SVM analyses with response on treatment (yes/no) as the outcome variable. Results:Baseline (AUC = 0.99) and 12-month (AUC = 0.99) predictive biomarker profiles were highly accurate in predicting response on Celecoxib arm at 12 and 24 months. The baseline (AUC = 0.95) and 12-month (AUC = 0.9) predictive biomarker profile predicting response on Naproxen were also highly accurate at 12 and 24 months. The baseline (AUC = 0.93) and 12-month (AUC = 0.99) predictive biomarker profile was also highly accurate in predicting response on placebo. As with our prior work, the profiles varied by treatment arm. Conclusions:The current results provide additional support for a precision medicine model for treating and preventing Alzheimer’s disease.

Keywords: Alzheimer’s disease, bioinformatics, biomarkers, clinical trial, inflammation, precision medicine, prevention, proteomics

DOI: 10.3233/JAD-230317

Journal: Journal of Alzheimer's Disease, vol. 95, no. 4, pp. 1609-1622, 2023