Diagnosis of dementia by measuring proteins in blood

Lead investigator: Dr Elizabeta Mukaetova-Ladinska

Institution: Newcastle University

Grant type: Project

Duration: 18 months

Start Date: April 2013

Completion Date: September 2014

Amount: £86,237

Scientific Title: Diagnosis of dementia by measuring proteins in blood

What was the project, and what did the researchers do?

Current methods of diagnosing dementia require a range of clinical tests and it can sometimes be difficult to distinguish between the different forms of the condition. The only way to fully confirm a particular type of dementia is to look at changes in the brain after death.

However, for certain types of dementia, including Alzheimer's disease and dementia with Lewy bodies, certain proteins build up in the brain and it might be possible to detect these proteins in the blood or spinal fluid. The proteins are called amyloid and tau in Alzheimer's disease, and alpha-synuclein in dementia with Lewy bodies.

The researchers were aiming to identify proteins that could be used as markers in a blood test for dementia. They hope that a blood test such as this would be able to distinguish between the different types of dementia more accurately than existing diagnostic methods. It could also provide benefits for future clinical trials as it could be used to measure the effect of new treatments on the levels of these dementia-related proteins. 

The study recruited 100 volunteers, 50 of whom had been diagnosed with dementia, the other 50 were of the same average age but were not diagnosed with memory problems. The volunteers gave a blood sample when the study began and then again six months later. The researchers measured the levels of a number of proteins in the blood samples and determined if there were any proteins that had different levels in those with dementia compared to those without. 

What were the key results, and how will this help in the fight against dementia

The study identified several proteins found in blood that show different levels in those affected by dementia. One of these proteins was a form of the Alzheimer’s hallmark protein tau, called tau-C. Tau-C levels were slightly higher in people who had mild cognitive impairment or early dementia symptoms.

Other proteins were also identified that could potentially be used as markers of the condition; these were TLR1, TLR2, TLR4, MyD88 and CD14. The researchers also found that a protein called alpha-synuclein hexamer is found at lower levels in people with dementia. Those affected by vascular dementia were found to have even lower levels of this protein than those with Alzheimer’s disease.

The researchers are currently developing methods to more accurately measure these proteins in blood samples. This will ensure that any results given by a blood test such as this would be as accurate as possible. 

These preliminary results are a step forward in finding a more effective way to diagnose particular types of dementia. If the accuracy of the technique can be sufficiently improved, then it would enable those affected to access the correct information, support and treatments regarding their particular condition. 

What happened next? Future work and additional grants

The analysis of the samples is still ongoing. The researchers then hope to expand the study over a longer time-frame to improve the accuracy of the test. 

The methods the researchers are developing to analyse blood proteins also have the potential to be developed into a tool that can be used in a hospital setting. The researchers received an award from the Engineering and Physical Sciences Research Council (EPSRC) in order to further develop this idea. 

How were people told about the results? Conferences and publications

Papers

Mukaetova-Ladinska EB, Abdel-All Z, Andrade J, Alves da Silva J, O'Brien JT, Kalaria RN. Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study. Int J Geriatr Psychiatry. 2014 Jun 12. doi: 10.1002/gps.4145.

Mukaetova-Ladinska EB, Krsteska R, Vaskova O, Makazlieva T, Tsolaki M. Dementia and depression in older adults: a southeast European perspective: summary of a dementia psychogeriatric symposium held in Ohrid, Macedonia, 23 May 2013. J Alzheimers Dis. 2014;41(4):1251-60.

Mukaetova-Ladinska EB, Boksha I: Is leptin a biomarker for dementia? Age and Ageing 2015 44(1):4-6.

Boksha IS, Gavrilova SI, Kolykhalov IV, Fedorova YaB, Kalyn YaB, Selezneva ND. Samorodov AV, Miasoedov SN, Mukaetova-Ladinska EB. Progression of Cognitive Deficit in Older People with Mild Cognitive Impairment Treated with Cerebrolysin. Health, 2014  6, 2581-2591

Mukaetova-Ladinska EB: Molecular Imaging Biomarkers for Dementia with Lewy Bodies: An Update. International Psychogeriatrics. 2015 Apr;27(4):555-77

Mukaetova-Ladinska EB, Abdel-All Z, Santiago Mugica E, Li M, Craggs LJL,  Oakley AE, Honer WG, Kalaria RN. Tau proteins in the temporal and frontal cortices in vascular dementia JNEN. 2015 Feb;74(2):148-57.