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

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

Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2023
Historique:
pubmed: 18 9 2023
medline: 18 9 2023
entrez: 18 9 2023
Statut: ppublish

Résumé

The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was the first-ever large-scale anti-inflammatory prevention trial targeting Alzheimer's disease. 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. 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. 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. The current results provide additional support for a precision medicine model for treating and preventing Alzheimer's disease.

Sections du résumé

BACKGROUND 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 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 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 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 CONCLUSIONS
The current results provide additional support for a precision medicine model for treating and preventing Alzheimer's disease.

Identifiants

DOI: 10.3233/JAD-230317 PMID: 37718801
pubmed: 37718801
pii: JAD230317
doi: 10.3233/JAD-230317
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1609-1622

Auteurs

Sid E O'Bryant (SE)

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.

Fan Zhang (F)

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.

Leigh A Johnson (LA)

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.

James Hall (J)

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.

Melissa Petersen (M)

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.

Esther S Oh (ES)

Department of Medicine, Johns Hopkins School of Medicine, Baltimore, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Constantine G Lyketsos (CG)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Robert A Rissman (RA)

Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA.
VA San Diego Healthcare System, San Diego, CA, USA.

Classifications MeSH