Written in blood: Plasma biomarkers could aid AD diagnosis

In the continued efforts to identify peripheral biomarkers of Alzheimer’s disease (AD), a group of Australian researchers has published promising results in the area of blood-based protein biomarkers. The researchers identified a panel of plasma biomarkers that could help distinguish individuals with AD from cognitively healthy individuals with high sensitivity and specificity, according to a study published online July 16 in Archives of Neurology.

The most promising source of validated AD biomarkers comes from cerebrospinal fluid (CSF) analysis, explained study authors James D. Doecke, PhD, of Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia, and colleagues. Recently, however, studies of blood-based proteins have demonstrated a number of benefits.

“Compared with CSF, blood analysis has advantages as an approach to population-based disease screening because it is simpler and less invasive,” wrote the authors. “As such, there has been strong interest in obtaining usable blood-based biomarkers for AD diagnosis.”

In the current study, Doecke and colleagues performed statistical analyses of a large biomarker set from the Australian Imaging Biomarker and Lifestyle (AIBL) study and validated the results with data from the Alzheimer Disease Neuroimaging Initiative (ADNI) study. The AIBL cohort featured 207 participants with AD and 754 healthy control subjects, while the ADNI cohort consisted of 112 individuals with AD and 58 healthy controls. Variable selection approaches were conducted independently, with biomarkers chosen for further analysis if they were selected in each variable selection method.

Results showed that of all the biomarkers identified, cortisol, insulinlike growth factor binding protein 2 (IGFBP2) and pancreatic polypeptide (PPY) were the ones most frequently chosen. In addition to these three, interleukin 17 (IL-17), vascular cell adhesion molecule 1 (VCAM1), Beta₂ microglobulin (B2M), epidermal growth factor receptor (EGFR) and carcinoembryonic antigen were found to be part of a blood-based signature to identify AD, according to the authors. Cross-validation with the AIBL cohort resulted in a mean of 85 percent for sensitivity and 93 percent for specificity for the area under the receiver operating characteristic curve. Subsequent validation using the ADNI cohort resulted in a sensitivity and specificity of 80 percent and 85 percent, respectively.

“The biomarkers identified in this cross-sectional analysis of data from the AIBL study may contribute toward the development of a blood-based diagnostic test, which together with appropriate imaging phenotypes may deliver an accurate means to diagnose AD,” wrote the authors.

Doecke et al noted that it remains to be determined whether the accuracy of the panel of biomarkers could be improved in combination with biomarkers identified in other recent studies.