Proteins Predict Alzheimer's Disease Risk in Patients with Mild Cognitive Disorder

A blood test that measures a panel of three complement proteins was shown to predict which individuals with a mild cognitive disorder would most likely progress to develop Alzheimer's disease (AD).

The growing appreciation of the importance of inflammation in early AD has focused attention on inflammatory biomarkers in cerebrospinal fluid or plasma; however, the measurement of non-specific inflammation markers has not shown great success. For this reason, investigators at Cardiff University (United Kingdom) and other institutions in the United Kingdom adopted a targeted approach, centered on an inflammatory pathway already implicated in the disease.


The investigators analyzed five complement proteins and four activation products in blood samples taken from 292 individuals with the earliest signs of memory impairment. They found that only one complement analyte, clusterin, differed significantly between controls and plasma from patients who had gone on to develop AD.

Clusterin (apolipoprotein J) is a protein associated with the clearance of cellular debris and apoptosis. In humans, clusterin is encoded by the CLU gene on chromosome eight. It is a molecular chaperone responsible for aiding protein folding of secreted proteins, and its three isoforms have been differentially implicated in pro- or antiapoptotic processes. Through this function, CLU is involved in many diseases related to oxidative stress, including neurodegenerative diseases, cancers, inflammatory diseases, and aging.

A model combining clusterin with relevant co-variables was found to be highly predictive of AD risk. Three analytes (clusterin, factor I, and terminal complement complex) were significantly different between individuals with mild cognitive impairment who had progressed to AD one year later compared to those that did not. A model combining these three analytes with informative co-variables was highly predictive of AD risk.

"Senior author Dr. B. Paul Morgan, professor of infection and immunity at Cardiff University, said, "Alzheimer's disease affects around 520,000 people in the United Kingdom and this number is continually growing as the population ages. As such it is important that we find new ways to diagnose the disease early, giving us a chance to investigate and instigate new treatments before irreversible damage is done. Our research proves that it is possible to predict whether or not an individual with mild memory problems is likely to develop Alzheimer's disease over the next few years. 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."

The study was published in the August 2016 online edition of the Journal of Alzheimer's Disease.

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