Nanoscale microanalysis of bile pigments for the diagnosis and prognosis of disabling neurological diseases

Mild cognitive impairment (MCI) and Alzheimer disease (AD) are linked to the early biochemical changes prior to the evident neurodegeneration. Although cerebrospinal fluid (CSF) biological biomarkers offer strong biological characterization of AD, they cannot be used on large scale and repeatedly due to their invasive collection. Bilirubin metabolism, influenced by genetic variation in transporters and enzymes, has been implicated in oxidative stress, neuroprotection and blood–brain barrier function, but its potential role as a peripheral biomarker in AD remains inadequately explored. The research problem was to examine whether fractionated bilirubinaemia could be used as an ancillary peripheral biomarker of AD and MCI, and to check the effects of genetic polymorphisms in the bilirubin transporters and metabolizing enzymes on bilirubin fractions and cognitive status. The selected polymorphisms in bilirubin transporters were genotyped in patients with AD, MCI with AD and MCI without AD. The HUG assay was used to measure serum bilirubin fractions, unconjugated and conjugated bilirubin. The bilirubin fraction, genetic variation, and ability of cognitive performance were compared. The results indicate that fractionated bilirubinaemia along with genetic profiling can contribute biologically meaningful and minimally intrusive adjunct biomarker of Alzheimer disease and mild cognitive impairment. This strategy could be used together with well-known biomarkers and help to increase the risk stratification and characterization of the disease.