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Alzheimer’s disease progression linked to changing protein levels in immune system

December 16, 2015
New research has identified changing levels of proteins in the blood which are associated with increasing mental impairment over time in people with Alzheimer's disease. The findings could ultimately help develop new drugs for the condition, by allowing better monitoring of the effects of drugs and improvements in clinical trials.

Diagnosis of Alzheimer’s disease is currently based on assessment of an individual’s cognitive decline. However, substantial changes to a person’s brain have already occurred by the time they start to show these symptoms, so an intensive research effort is currently underway to identify biological markers (biomarkers) which can accurately detect Alzheimer’s disease before it has progressed far enough to cause noticeable symptoms.

In this study, Dr Martina Sattlecker, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) in London, and colleagues investigated if blood protein changes over time are associated with the rate of cognitive decline in people with Alzheimer’s disease.

The researchers analysed 1,001 proteins in blood samples from 235 people, over a third of whom had confirmed Alzheimer’s disease.  Other participants had stable mild cognitive impairment, mild cognitive impairment which developed to Alzheimer’s disease within a year, or were in a control group.

The analysis, which is published in the Journal of Alzheimer’s Disease, allowed the researchers to identify proteins which changed significantly over one year with the rate of cognitive decline.  They found that levels of proteins in part of the immune system called the complement cascade increased significantly in people with Alzheimer’s disease who experienced rapid cognitive decline, suggesting that changes in the complement cascade might be a surrogate biomarker for disease progression.

According to Dr Sattlecker, “Alzheimer’s disease is a devastating illness, and to date, there is no cure.  The medication currently available can only temporarily alleviate some symptoms or slow down progression in a subset of patients, so new drugs are urgently needed. To advance the development of disease modifying drugs, biomarkers for early diagnosis and disease progression are required.  A biomarker capable of predicting disease progression would aid drug development.

The biomarkers we have identified in this study will need to be further tested in order to assess if they are suitable for clinical application.  The next step is to investigate the changing protein levels we observed here over a longer time frame in a larger group of patients.”

The research was partly supported by the NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and Kings College London. The other funders of the study were InnoMed (Innovative Medicines in Europe), an Integrated Project funded by the European Union of the Sixth Framework program priority; the Alzheimer’s Research Trust; The John and Lucille van Geest Foundation and, and a joint infrastructure grant from Guy’s and St Thomas’  Charity and the Maudsley Charity; Kuopio University Hospital and funding from UEFBRAIN.

Paper reference: Sattlecker, M et al (2015), Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease, DOI: 10.3233/JAD-140669, Journal of Alzheimer’s Disease