Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis

Petroula Proitsi; Min Kim; Luke Whiley; Andrew Simmons; Martina Sattlecker; Latha Velayudhan; Michelle K Lupton; Hillka Soininen; Iwona Kloszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone; John F Powell; Richard J B Dobson; Cristina Legido-Quigley

doi:10.1016/j.jalz.2016.08.003

Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis

Petroula Proitsi, Min Kim, Luke Whiley, Andrew Simmons, Martina Sattlecker, Latha Velayudhan, Michelle K Lupton, Hillka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Simon Lovestone, John F Powell, Richard J B Dobson, Cristina Legido-Quigley

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Abstract

INTRODUCTION: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).

METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.

RESULTS: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R(2) = 0.10, test data set) and brain atrophy (R(2) ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.

DISCUSSION: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.

Original language	English
Pages (from-to)	140-151
Number of pages	12
Journal	Alzheimer's & Dementia
Volume	13
Issue number	2
Early online date	28 Sept 2016
DOIs	https://doi.org/10.1016/j.jalz.2016.08.003
Publication status	Published - 28 Sept 2016

Keywords

Alzheimer's disease
Dementia
Brain atrophy
sMRI
Rate of cognitive decline
Lipidomics
Metabolomics
Biomarkers
Machine learning
Multivariate
Classification
Random forest

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Proitsi, P., Kim, M., Whiley, L., Simmons, A., Sattlecker, M., Velayudhan, L., Lupton, M. K., Soininen, H., Kloszewska, I., Mecocci, P., Tsolaki, M., Vellas, B., Lovestone, S., Powell, J. F., Dobson, R. J. B., & Legido-Quigley, C. (2016). Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis. Alzheimer's & Dementia, 13(2), 140-151. https://doi.org/10.1016/j.jalz.2016.08.003

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title = "Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis",

abstract = "INTRODUCTION: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.RESULTS: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R(2) = 0.10, test data set) and brain atrophy (R(2) ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.DISCUSSION: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.",

keywords = "Alzheimer's disease, Dementia, Brain atrophy, sMRI, Rate of cognitive decline, Lipidomics, Metabolomics, Biomarkers, Machine learning, Multivariate, Classification, Random forest",

author = "Petroula Proitsi and Min Kim and Luke Whiley and Andrew Simmons and Martina Sattlecker and Latha Velayudhan and Lupton, {Michelle K} and Hillka Soininen and Iwona Kloszewska and Patrizia Mecocci and Magda Tsolaki and Bruno Vellas and Simon Lovestone and Powell, {John F} and Dobson, {Richard J B} and Cristina Legido-Quigley",

year = "2016",

month = sep,

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doi = "10.1016/j.jalz.2016.08.003",

language = "English",

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Proitsi, P , Kim, M , Whiley, L , Simmons, A , Sattlecker, M , Velayudhan, L, Lupton, MK, Soininen, H, Kloszewska, I, Mecocci, P, Tsolaki, M, Vellas, B, Lovestone, S, Powell, JF , Dobson, RJB & Legido-Quigley, C 2016, 'Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis', Alzheimer's & Dementia, vol. 13, no. 2, pp. 140-151. https://doi.org/10.1016/j.jalz.2016.08.003

TY - JOUR

T1 - Association of blood lipids with Alzheimer's disease

T2 - A comprehensive lipidomics analysis

AU - Proitsi, Petroula

AU - Kim, Min

AU - Whiley, Luke

AU - Simmons, Andrew

AU - Sattlecker, Martina

AU - Velayudhan, Latha

AU - Lupton, Michelle K

AU - Soininen, Hillka

AU - Kloszewska, Iwona

AU - Mecocci, Patrizia

AU - Tsolaki, Magda

AU - Vellas, Bruno

AU - Lovestone, Simon

AU - Powell, John F

AU - Dobson, Richard J B

AU - Legido-Quigley, Cristina

PY - 2016/9/28

Y1 - 2016/9/28

N2 - INTRODUCTION: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.RESULTS: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R(2) = 0.10, test data set) and brain atrophy (R(2) ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.DISCUSSION: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.

AB - INTRODUCTION: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.RESULTS: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R(2) = 0.10, test data set) and brain atrophy (R(2) ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.DISCUSSION: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.

KW - Alzheimer's disease

KW - Dementia

KW - Brain atrophy

KW - sMRI

KW - Rate of cognitive decline

KW - Lipidomics

KW - Metabolomics

KW - Biomarkers

KW - Machine learning

KW - Multivariate

KW - Classification

KW - Random forest

U2 - 10.1016/j.jalz.2016.08.003

DO - 10.1016/j.jalz.2016.08.003

M3 - Article

C2 - 27693183

SN - 1552-5260

VL - 13

SP - 140

EP - 151

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 2

ER -

Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis

Abstract

Keywords

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