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
ɛ4 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 replication, further studies are required.
