A metabolite-based machine learning approach to diagnose Alzheimer’s-type dementia in blood: Results from the European Medical Information Framework for Alzheimer’s Disease biomarker discovery cohort

Stamate, Daniel; Kim, Min; Proitsi, Petroula; Westwood, Sarah; Baird, Alison; Nevado-Holgado, Alejo; Hye, Abdul; Bos, Isabelle; Vos, Stephanie; Vandenberghe, Rik; Teunissen, Charlotte; Kate, Mara Ten; Scheltens, Philip; Gabel, Silvy; Meersmans, Karen; Blin, Olivier; Richardson, Jill; Roeck, Ellen De; Engelborghs, Sebastiaan; Sleegers, Kristel; Bordet, Régis; Rami, Lorena; Kettunen, Petronella; Tsolaki, Magda; Verhey, Frans; Alcolea, Daniel; Lléo, Alberto; Peyratout, Gwendoline; Tainta, Mikel; Johannsen, Peter; Freund-Levi, Yvonne; Frölich, Lutz; Dobricic, Valerija; Frisoni, Giovanni; Molinuevo, José; Wallin, Anders; Popp, Julius; Martinez-Lage, Pablo; Bertram, Lars; Blennow, Kaj; Zetterberg, Henrik; Streffer, Johannes; Visser, Pieter; Lovestone, Simon; Legido-Quigley, Cristina

doi:10.1101/19007146

Author:

Stamate, Daniel

Kim, Min ; Proitsi, Petroula ; Westwood, Sarah ; Baird, Alison ; Nevado-Holgado, Alejo ; Hye, Abdul ; Bos, Isabelle ; Vos, Stephanie ; Vandenberghe, Rik ; Teunissen, Charlotte ; Kate, Mara Ten ; Scheltens, Philip ; Gabel, Silvy ; Meersmans, Karen ; Blin, Olivier ; Richardson, Jill ; Roeck, Ellen De ; Engelborghs, Sebastiaan ; Sleegers, Kristel ; Bordet, Régis ; Rami, Lorena ; Kettunen, Petronella ; Tsolaki, Magda ; Verhey, Frans ; Alcolea, Daniel ; Lléo, Alberto ; Peyratout, Gwendoline ; Tainta, Mikel ; Johannsen, Peter ; Freund-Levi, Yvonne ; Frölich, Lutz ; Dobricic, Valerija ; Frisoni, Giovanni ; Molinuevo, José ; Wallin, Anders ; Popp, Julius ; Martinez-Lage, Pablo ; Bertram, Lars ; Blennow, Kaj ; Zetterberg, Henrik ; Streffer, Johannes ; Visser, Pieter ; Lovestone, Simon ; Legido-Quigley, Cristina

Abstract:

INTRODUCTION

Machine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer’s Disease (AD). Here we set out to test the performance of metabolites in blood to categorise AD when compared to CSF biomarkers.

METHODS

This study analysed samples from 242 cognitively normal (CN) people and 115 with AD-type dementia utilizing plasma metabolites (n=883). Deep Learning (DL), Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were used to differentiate AD from CN. These models were internally validated using Nested Cross Validation (NCV).

RESULTS

On the test data, DL produced the AUC of 0.85 (0.80-0.89), XGBoost produced 0.88 (0.86-0.89) and RF produced 0.85 (0.83-0.87). By comparison, CSF measures of amyloid, p-tau and t-tau (together with age and gender) produced with XGBoost the AUC values of 0.78, 0.83 and 0.87, respectively.

DISCUSSION

This study showed that plasma metabolites have the potential to match the AUC of well-established AD CSF biomarkers in a relatively small cohort. Further studies in independent cohorts are needed to validate whether this specific panel of blood metabolites can separate AD from controls, and how specific it is for AD as compared with other neurodegenerative disorders