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Blood Protein Markers of Neocortical Amyloid-β Burden: A Candidate Study Using SOMAscan Technology.

Research output: Contribution to journalArticle

Nicola Voyle ; David Baker ; Samantha C Burnham ; Antonia Covin ; Zhanpan Zhang ; Dipen P Sangurdekar ; Hehir CA Tan ; Chantal Bazenet ; Simon Lovestone ; Steven Kiddle ; Richard James Butler Dobson

Original languageUndefined/Unknown
Pages (from-to)947-961
Number of pages15
JournalJOURNAL OF ALZHEIMERS DISEASE
Volume46
Issue number4
Early online date16 Apr 2015
DOIs
StatePublished - 26 Jun 2015

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Abstract

BACKGROUND:
Four previously reported studies have tested for association of blood proteins with neocortical amyloid-β burden (NAB). If shown to be robust, these proteins could have utility as a blood test for enrichment in clinical trials of Alzheimer's disease (AD) therapeutics.
OBJECTIVE:
This study aimed to investigate whether previously identified blood proteins also show evidence for association with NAB in serum samples from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL). The study considers candidate proteins seen in cohorts other than AIBL and candidates previously discovered in the AIBL cohort.
METHODS:
Our study used the SOMAscan platform for protein quantification in blood serum. Linear and logistic regressions were used to model continuous NAB and dichotomized NAB respectively using single proteins as a predictor. Multiple protein models were built using stepwise regression techniques and support vectors machines. Age and APOE ε4 carriage were used as covariates for all analysis.
RESULTS:
Of the 41 proteins previously reported, 15 AIBL candidates and 20 non-AIBL candidates were available for testing. Of these candidates, pancreatic polypeptide (PPY) and IgM showed a significant association with NAB. Notably, IgM was found to associate with continuous NAB across cognitively normal control subjects.
CONCLUSIONS:
We have further demonstrated the association of PPY and IgM with NAB, despite technical differences between studies. There are several reasons for a lack of significance for the other candidates including platform differences and the use of serum rather than plasma samples. To investigate the possibility of technical differences causing lack of further replication, further studies are required.

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