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Prof Henrik Zetterberg, a Group Leader at our centre at UCL, is part of a team at the University of Gothenburg that has developed a new blood test for Alzheimer’s disease. 

The test measures a specific variant of tau protein in ordinary blood samples, making it relatively simple and cheap to perform.

The research behind the test was led by Kaj Blennow, Professor of Clinical Neurochemistry at Sahlgrenska Academy, University of Gothenburg, and Prof Zetterberg, who, in addition to his role at the UK DRI, is Professor of Neurochemistry at the Academy. The results were published today in the journal Lancet Neurology.

“Alzheimer’s disease is one of the greatest health challenges we face today, affecting tens of millions of people worldwide. Detecting the disease at the earliest possible stage is essential to combating its effects and to furthering our understanding of this devastating illness. By diagnosing early, we can better understand how it progresses, plan and implement treatments earlier, and monitor how the disease responds to drugs currently being trialled,” commented Prof Zetterberg.

Alzheimer’s disease is characterised by two pathological changes in the tissue of the nervous system. One is the formation of extracellular clumps of a protein called amyloid beta. The other is neurofibrils, composed of tau protein, that have stuck together in tiny lesions (neurofibrillary tangles) in brain neurons through a biochemical process known as phosphorylation.

The new test is based on measurement of phosphorylated tau — specifically, the P-tau181 variant — in ordinary blood samples, performed with an ultrasensitive method known as Single Molecule Array (Simoa). Simoa can detect considerably smaller quantities of protein biomarkers than other analytical methods.

“Until now, all methods developed for testing would be difficult or costly to implement on a large scale. A blood test is a significant step forward both in terms of advancing further study of the illness and improving people’s lives,” continued Prof Zetterberg.

High sensitivity and precision

P-tau181 has long been measurable through testing of cerebrospinal fluid, in which it is found at a considerably higher level than in blood samples. For the past few years, it has also been possible to demonstrate neurofibrils by using the advanced positron emission tomography (PET) medical imaging technique. Tests of cerebrospinal fluid are, however, difficult to perform in primary care, and the high costs of PET scans restrict their use. Being able to establish tau pathology through ordinary blood tests will therefore be highly valuable.

The results published today show that the level of P-tau181 is significantly elevated in Alzheimer’s disease, including at its early stage, known as mild cognitive impairment. However, this raised level was found only in people who also had amyloid plaques, as revealed by a PET scan.

The level of specific P-tau181 in blood plasma also proved to correspond very closely with the level of tau tangles in the brain registered with the PET-technique. The blood test also identified people early on in the course of the disease who had plaques, but in whom the PET technique discerned no increased tau levels.

The blood test showed a very good capacity to distinguish Alzheimer’s disease from other brain diseases, such as frontotemporal dementia and Parkinson’s disease, where the blood level of P-tau181 was entirely normal. 

“We are now establishing this method in UK DRI labs and using it to gain valuable new data from different cohorts. We hope to share our findings very soon,” added Prof Zetterberg.

Reference

Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts Karikari, Thomas K et al. The Lancet Neurology, Volume 19, Issue 5, 422 - 433

Article published: 23 April 2020