Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning

Early detection of Alzheimer's disease is essential for effective treatment and the development of therapies that modify disease progression. Developing sensitive and specific noninvasive diagnostic tools is crucial for improving clinical outcomes and advancing our understanding of this conditi...

Full description

Saved in:
Bibliographic Details
Main Authors: Ali Safi, Elisa Giunti, Omar Melikechi, Weiming Xia, Noureddine Melikechi
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844025007297
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832542465249247232
author Ali Safi
Elisa Giunti
Omar Melikechi
Weiming Xia
Noureddine Melikechi
author_facet Ali Safi
Elisa Giunti
Omar Melikechi
Weiming Xia
Noureddine Melikechi
author_sort Ali Safi
collection DOAJ
description Early detection of Alzheimer's disease is essential for effective treatment and the development of therapies that modify disease progression. Developing sensitive and specific noninvasive diagnostic tools is crucial for improving clinical outcomes and advancing our understanding of this condition. Liquid biopsy techniques, especially those involving plasma biomarkers, provide a promising noninvasive method for early diagnosis and disease monitoring. In this study, we analyzed the plasma proteomic profiles of 38 healthy individuals, with an average age of 66.5 years, and 22 patients with Alzheimer's disease, with an average age of 79.7 years. Proteins in the plasma were quantified using specialized panels designed for proteomic extension assays. Through computational analysis using a linear support vector machine algorithm, we identified 82 differentially expressed proteins between the two groups. From these, we calculated 6642 possible protein ratios and identified specific combinations of these ratios as significant features for distinguishing between individuals with Alzheimer's disease and healthy individuals. Notably, the protein ratios kynureninase to macrophage scavenger receptor type 1, Neurocan to protogenin, and interleukin-5 receptor alpha to glial cell line-derived neurotrophic factor receptor alpha 1 achieving accuracy up to 98 % in differentiating between the two groups. This study underscores the potential of leveraging protein relationships, expressed as ratios, in advancing Alzheimer's disease diagnostics. Furthermore, our findings highlight the promise of liquid biopsy techniques as a noninvasive and accurate approach for early detection and monitoring of Alzheimer's disease using blood plasma.
format Article
id doaj-art-aa92e6bcb1ee4db18d0f9d9ae0c73ef1
institution Kabale University
issn 2405-8440
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series Heliyon
spelling doaj-art-aa92e6bcb1ee4db18d0f9d9ae0c73ef12025-02-04T04:10:30ZengElsevierHeliyon2405-84402025-02-01113e42349Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learningAli Safi0Elisa Giunti1Omar Melikechi2Weiming Xia3Noureddine Melikechi4Kennedy College of Sciences, University of Massachusetts Lowell, Lowell, MA, 01854, USABedford VA Healthcare System, Bedford, MA, 01730, USA; Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USAKennedy College of Sciences, University of Massachusetts Lowell, Lowell, MA, 01854, USA; Bedford VA Healthcare System, Bedford, MA, 01730, USA; Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USAKennedy College of Sciences, University of Massachusetts Lowell, Lowell, MA, 01854, USA; Corresponding author.Noureddine_Melikechi@uml.eduEarly detection of Alzheimer's disease is essential for effective treatment and the development of therapies that modify disease progression. Developing sensitive and specific noninvasive diagnostic tools is crucial for improving clinical outcomes and advancing our understanding of this condition. Liquid biopsy techniques, especially those involving plasma biomarkers, provide a promising noninvasive method for early diagnosis and disease monitoring. In this study, we analyzed the plasma proteomic profiles of 38 healthy individuals, with an average age of 66.5 years, and 22 patients with Alzheimer's disease, with an average age of 79.7 years. Proteins in the plasma were quantified using specialized panels designed for proteomic extension assays. Through computational analysis using a linear support vector machine algorithm, we identified 82 differentially expressed proteins between the two groups. From these, we calculated 6642 possible protein ratios and identified specific combinations of these ratios as significant features for distinguishing between individuals with Alzheimer's disease and healthy individuals. Notably, the protein ratios kynureninase to macrophage scavenger receptor type 1, Neurocan to protogenin, and interleukin-5 receptor alpha to glial cell line-derived neurotrophic factor receptor alpha 1 achieving accuracy up to 98 % in differentiating between the two groups. This study underscores the potential of leveraging protein relationships, expressed as ratios, in advancing Alzheimer's disease diagnostics. Furthermore, our findings highlight the promise of liquid biopsy techniques as a noninvasive and accurate approach for early detection and monitoring of Alzheimer's disease using blood plasma.http://www.sciencedirect.com/science/article/pii/S2405844025007297Alzheimer's diseaseLiquid biopsyBlood plasmaProteomicsMachine learning
spellingShingle Ali Safi
Elisa Giunti
Omar Melikechi
Weiming Xia
Noureddine Melikechi
Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
Heliyon
Alzheimer's disease
Liquid biopsy
Blood plasma
Proteomics
Machine learning
title Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
title_full Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
title_fullStr Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
title_full_unstemmed Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
title_short Identification of blood plasma protein ratios for distinguishing Alzheimer's disease from healthy controls using machine learning
title_sort identification of blood plasma protein ratios for distinguishing alzheimer s disease from healthy controls using machine learning
topic Alzheimer's disease
Liquid biopsy
Blood plasma
Proteomics
Machine learning
url http://www.sciencedirect.com/science/article/pii/S2405844025007297
work_keys_str_mv AT alisafi identificationofbloodplasmaproteinratiosfordistinguishingalzheimersdiseasefromhealthycontrolsusingmachinelearning
AT elisagiunti identificationofbloodplasmaproteinratiosfordistinguishingalzheimersdiseasefromhealthycontrolsusingmachinelearning
AT omarmelikechi identificationofbloodplasmaproteinratiosfordistinguishingalzheimersdiseasefromhealthycontrolsusingmachinelearning
AT weimingxia identificationofbloodplasmaproteinratiosfordistinguishingalzheimersdiseasefromhealthycontrolsusingmachinelearning
AT noureddinemelikechi identificationofbloodplasmaproteinratiosfordistinguishingalzheimersdiseasefromhealthycontrolsusingmachinelearning