June 10, 2015

expert reaction to proteins in blood may help detect Alzheimer’s

The use of blood tests to diagnose specific diseases is a vital tool in modern medicine, and researchers publishing in the journal Neurology have described their early attempts to look for markers which could one day be used in a test for Alzheimer’s. Using a small group of a few dozen patients, the team report that they were able use presence of specific proteins to distinguish between patients with and without Alzheimers, up to ten years before onset of disease.

Dr Mark Dallas, Lecturer in Cellular and Molecular Neuroscience, University of Reading, said:

“This study highlights the potential to detect blood borne changes in Alzheimer’s patients prior to clinical symptoms developing. This is a current challenge within the field of dementia research – one that if successfully achieved would allow us to target individuals for vital clinical trials.

“The small sample size limits our interpretation of the current study. It also raises some questions with regards to distinct types of dementia showing different biological fingerprints. Although not the breakthrough we are waiting for, it offers hope that this type of research, if repeated in a larger sample size, could uncover more of the biological complexities of Alzheimer’s disease.”

Dr Tara Spires-Jones, Chancellor’s Fellow and Reader, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“The brain begins to change long before any detectable symptoms appear in Alzheimer’s patients. Treating people during this preclinical stage has great potential for preventing dementia, but at the moment we cannot accurately determine whether people are healthy or if they are in the preclinical stages of dementia.

“The paper by Goetzl and colleagues published today in the journal Neurology is working towards the goal of a reliable biomarker to detect the earliest stages of disease. Authors found a marker in blood that could distinguish people with AD from healthy controls up to 10 years before diagnosis; however, this study was conducted on a small group of people and needs to be replicated in larger groups.

“If a larger study confirms the predictive relevance of these markers, it will be a fantastic tool for directing people to clinical trials early in the disease process. While this study is promising, caution should be taken to not interpret the results as a fool proof ‘blood test for Alzheimer’s’ at this stage.”

Prof. Carol Brayne, Professor of Public Health Medicine, University of Cambridge, said:

“Most people aged over 80 have some Alzheimer’s type pathology in their brains. A substantial number of these will die without ever having developed dementia. A test at earlier stages of life might well detect people who would not benefit from this information, even if there was an effective treatment for the biology as it might not change the person’s natural history as they aged. Future treatments will almost certainly have harms as well as benefits, as do pretty well all other medications.

“For a test like this to predict Alzheimer’s it would need to be conducted on people who do not have symptoms and therefore a younger population would need to be screened – for a test to fulfil screening criteria for this kind of use there is a very, very high standard to meet. Proponents of screening might say they’d use other information to stratify people at higher risk, but that too must be tested to see whether the higher risk is high enough to tolerate the imperfections of (any) screening test in terms of its ability to identify a known natural history (with known boundaries of potentially acceptable uncertainty for that person, that age, that context).

“How such tests are evaluated further for their true potential contribution to managing dementia in ageing societies needs very careful attention. For the time being it is important to be realistic about the potential and the meaning of all such findings. Further research is essential to answer these uncertainties”

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

“This is important as it suggests that altered blood proteins may be a marker of early Alzheimer’s disease, possibly 10 years before significant memory problems develop.

“It also gives us further insight into what might be going wrong in brain cells.

“However it is too soon to consider the results a breakthrough. These findings need to be checked in a larger number of subjects to be certain that the changes are sufficiently sensitive and specific to be used as a clinic test, and also whether they can predict which asymptomatic people will develop dementia in due course.”

Prof. John Hardy, Professor of Neuroscience, UCL, said:

“As the authors themselves say, ‘Numerous problems inherent in retrospective studies of small numbers of carefully selected patients suggest that conclusions of the preliminary investigations here reported may be modified by results of larger prospective analyses’.

“I think it is too soon for this to do more than alert other groups with similar samples to test these analyses in their sample sets.”

Dr Eric Karran, Director of Research, Alzheimer’s Research UK, said:

“This small study is one of an emerging research area that might hold real promise for early diagnosis of some neurodegenerative diseases. It needs to be confirmed in much larger groups of patients to ensure the findings reported are robust. The ability to accurately identify Alzheimer’s at the earliest stages would be a crucial step forward for research, as it’s likely that new treatments will have the best chance of success if given early. If confirmed in larger studies, these findings could enable the right people to be recruited for clinical trials, but this test is not designed for use in the doctor’s clinic.

“Research like this can also provide valuable clues about changes inside brain cells during Alzheimer’s, helping to guide efforts to develop new and effective treatments. Over half a million people are affected by Alzheimer’s in the UK today, and only through research will we be able to successfully fight the disease.”

‘Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease’ by Goetzl et al. published in Neurology on Wednesday 10^th June. 

Declared interests

Prof. Hardy: “I consult for Cytox on Alzheimer diagnosis.”

Others: No declarations received.