New Evidence Linking Clusterin and Other Complement Proteins to Alzheimer’s Progression and Prediction

dementia and Alzheimer's

A study recently published in the Journal of Alzheimer’s Disease gives hope in the search of Alzheimer’s biomarkers indicating that some complement factors such as clusterin may serve as reliable predictors of Alzheimer’s disease progression.

It is well known that inflammation and pro-inflammatory mediators contribute to the pathogenesis of dementia and Alzheimer’s. The complement system, part of the innate immunity and a potent driver of inflammation, “enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells”. Previous research also implicates this innate immune system in the development of Alzheimer’s disease.

In the Journal of Alzheimer’s Disease study, Svetlana Hakobyan and colleagues from Cardiff University, King’s College London and University of Oxford, UK, compared samples from individuals with Alzheimer’s and healthy matched controls. The authors also studied samples from individuals with mild cognitive impairment (MCI) who had subsequently converted to dementia, when re-assessed 12 months later (convertors), or who had remained stable over the period of assessment (non-convertors). The researchers also designed a multiplex assay to measure simultaneously ten complement analytes.

In this study, Hakobyan et al. report that clusterin alone among the analytes tested significantly differentiated AD patients from matched controls. On the other hand, clusterin, complement factor H (FH), and terminal complement complex (TCC), differed significantly between MCI convertors and non-convertors.

The study provides further evidence that complement proteins may contribute to disease progression in Alzheimer’s, and that combinations of complement biomarkers can aid diagnosis, patient stratification and prediction of outcome in MCI and Alzheimer’s disease.

Professor Paul Morgan, the senior author of the study, and director of Cardiff University’s Systems Immunity Research Institute, stated “We hope to build on this in order to develop a simple blood test that can predict the likelihood of developing Alzheimer’s disease in older people with mild, and possibly innocent, memory impairment.”

Source: J Alzheimers Dis. 2016 Sep 6;54(2):707-16. doi: 10.3233/JAD-160420.