Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's

Elaine Delvaux, Diego Mastroeni, Jennifer Nolz, Nienwen Chow, Marwan Sabbagh, Richard J. Caselli, Eric M. Reiman, Frederick J. Marshall, Paul Coleman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples. Rather than a single study with no replicates, we chose an experimental design in which there were multiple replicates using different platforms and different sample populations. We have divided 177 blood samples and 27 brain samples into multiple replicates to demonstrate the ability to distinguish early clinical AD (Clinical Dementia Rating scale 0.5), Parkinson's disease (PD), and cognitively unimpaired APOE4 homozygotes, as well as to determine persons at risk for future cognitive impairment with significant accuracy. We assess our methods in a training/test set and also show that the variables we use distinguish AD, PD, and control brain. Importantly, we describe the variability of the weights assigned to individual transcripts in multivariate analyses in repeated studies and suggest that the variability we describe may be the cause of inability to repeat many earlier studies. Our data constitute a proof of principle that multivariate analysis of the transcriptome related to cell stress and inflammation of peripheral blood leukocytes has significant potential as a minimally invasive and inexpensive diagnostic tool for diagnosis and early detection of risk for AD.

Original languageEnglish (US)
Pages (from-to)225-237
Number of pages13
JournalNeurobiology of Aging
Volume58
DOIs
StatePublished - Oct 1 2017

Fingerprint

Alzheimer Disease
Leukocytes
Multivariate Analysis
Hematologic Tests
Parkinson Disease
Aptitude
Brain
Homozygote
Oligonucleotide Array Sequence Analysis
Transcriptome
Dementia
Publications
Primary Health Care
Research Design
Inflammation
Weights and Measures
Polymerase Chain Reaction
Population
Genes

Keywords

  • Alzheimer's disease
  • Blood test
  • Prodromal detection
  • RNA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's. / Delvaux, Elaine; Mastroeni, Diego; Nolz, Jennifer; Chow, Nienwen; Sabbagh, Marwan; Caselli, Richard J.; Reiman, Eric M.; Marshall, Frederick J.; Coleman, Paul.

In: Neurobiology of Aging, Vol. 58, 01.10.2017, p. 225-237.

Research output: Contribution to journalArticle

Delvaux, Elaine ; Mastroeni, Diego ; Nolz, Jennifer ; Chow, Nienwen ; Sabbagh, Marwan ; Caselli, Richard J. ; Reiman, Eric M. ; Marshall, Frederick J. ; Coleman, Paul. / Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's. In: Neurobiology of Aging. 2017 ; Vol. 58. pp. 225-237.
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