July 8, 2014

expert reaction to biomarkers for Alzheimer’s

A group of researchers publishing in Alzheimer’s & Dementia looked at how accurate indicator proteins in people’s blood may be for predicting who is likely to develop the Alzheimer’s disease. A press briefing was held on the research.

Dr Adrian Pini, Non-clinical Senior Lecturer, MRC Centre for Developmental Neurobiology, King’s College London, said:

“The results reported today are interesting but as the authors point out there is still a very large amount of work remaining until a usable blood test for Alzheimer’s disease becomes available. The blood samples reported on in this paper were taken from three independent studies in Canada and Europe and it is critically important when trying to evaluate a potential diagnostic test that these populations are very precisely matched. For use in the NHS for example, the test’s predictive powers would need to be in the mid-nineties rather than the mid-eighties percent range and it is also a fairly complex test making it less easy to use on a large and practicable scale.”

Prof Gordon Wilcock, Emeritus Professor of Geratology, University of Oxford, said:

“This is great news! It is important confirmation that it will probably be feasible to use a blood protein test to help identify people with memory problems who will go on to develop dementia. It will also assist in measuring the severity of their disease.

“A blood test is much simpler and less invasive than testing cerebrospinal fluid obtained at lumbar puncture, and less troublesome to patients than having a brain scan.

“Although these findings require further verification they are nevertheless robust as they are based on samples from three different multicentre cohorts. If confirmed they will be of significant benefit in the design of trials of new treatments, and deciding which patients are more likely to respond to new drugs when these become available.”

Dr James Pickett, Head of Research, Alzheimer’s Society, said:

“Finding a way to detect dementia before symptoms develop would revolutionise research into the condition. Most of the blood proteins identified here are not new to the dementia community, but this study has brought them together into a protein set that seems to predict disease severity. Although it needs to be validated in a larger group of people, their modelling work shows a set of 10 proteins can predict which people with mild cognitive impairments will progress to developing dementia.

“However, this research does not mean that a blood test for dementia is just around the corner. These ten proteins can predict conversion to dementia with less than 90% accuracy, meaning one in ten people would get an incorrect result. Therefore, accuracy would need to be improved before it could be a useful diagnostic test. Only through further research will we find answers to the biggest questions around dementia, so we will watch the progress of this study with interest.”

Prof Peter Passmore, Professor of Ageing and Geriatric Medicine, Centre for Public Health, Queen’s University Belfast, said:

“The discovery of a test for Alzheimer’s Disease from a blood sample is a priority as this is the most acceptable form of testing for patients and carers. The study of people at the earliest stage of any dementia syndrome is also essential as it informs more about disease mechanisms and a more specific identification of people who progress to dementia will mean that the right people are recruited to clinical trials.

“Some caveats: I am unsure of the significance of some of the proteins mentioned as they only show a  trend towards reduced levels of the proteins RANTES, NSE and TTR in the mild cognitive impairment (MCI) group in relation to atrophy.

“The concept of MCI is well known in the clinic. The Petersen criteria are appropriate for use – within the MCI spectrum there are grades of progression to dementia – multi-domain amnestic MCI has a the highest risk of progression for example. A sub-classification of MCI in this way is relevant.

“A major factor in disease progression, either MCI-AD or in AD, is the amount of vascular damage in the brain and this was not measured. It is interesting that some of the proteins would seem to be related to the vasculature.

“Nevertheless this is an interesting development. The authors strongly make the point about the need for replication, best performed in prospective cohorts. They also clearly state that is unclear whether these proteins are specific to AD and that this needs tested.

“This study also provides signals about potential underlying mechanisms in dementia which is important in that it helps further our knowledge and directs further research.”

‘Plasma proteins predict conversion to dementia from prodromal disease’ by Hye et al. published in Alzheimer’s & Dementia on Tuesday 8^th July.

Declared interests

None declared