http://www.neurobiologyofaging.org/article/S0197-4580(17)30167-7/fulltext
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
Article InfoHighlights
- •Peripheral blood leukocyte transcripts can be used as a prognostic marker of progression to the clinical stages of Alzheimer’s disease in unimpaired older adults.
- •Peripheral blood leukocyte transcripts distinguish Parkinson’s disease from Alzheimer’s disease.
- •Peripheral blood leukocyte transcripts distinguish cognitively resilient apoe4 homozygotes.
- •The same peripheral blood leukocyte transcripts used to distinguish probable Alzheimer’s disease in blood samples were also able to distinguish neuropathologically confirmed Alzheimer’s disease in brain samples.
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 expression of selected sets of
genes followed by multivariate analyses in multiple independent samples.
Rather than one 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 and 27
brain samples into multiple replicates to demonstrate the ability to
distinguish early clinical AD (CDR 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 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 prior 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.
No comments:
Post a Comment