A blood test to detect two molecules that act as indicators of a person’s likelihood to get Alzheimer’s disease later in life has been hailed as a ‘potential game-changer’ in a new study.
The two molecules – P-tau181, a tau protein, and neurofilament light polypeptide (NfL) – are found in plasma, the light yellow liquid that makes up 55 per cent of our blood.
In a sample of 557 people in their 60s and 70s, the presence of P-tau181 and NfL were the two most accurate predictors of the progression from mild cognitive impairment (MCI) to severe memory and thinking problems, typical of Alzheimer’s.
Researchers say blood tests to detect the two molecules could allow doctors to track the progression of Alzheimer’s disease progression in at-risk populations.
The new study could help the development of routine blood tests to track Alzheimer’s disease progression in at-risk populations
‘Our study is novel in the way we address the individualised predictive value of plasma Alzheimer’s disease biomarkers,’ say the experts, from Lund University in Sweden.
‘Combination of plasma biomarkers may be of high value to identify individuals with MCI who will progress to Alzheimer’s in clinical trials and in clinical practice.’
Professor Masud Husain at University of Oxford, who was not involved in the study, called it a ‘potential gamechanger’.
‘For the first time, we have a blood test that can predict well the risk of subsequent development of Alzheimer’s disease in people who have mild cognitive symptoms,’ he said.
‘We need further validation but in the context of other recent findings this could be a transformative step to earlier diagnosis, as well as testing new treatments at earlier stages of the disease.’
The two molecules – P-tau181, a tau protein, and neurofilament light polypeptide (NfL) – are found in plasma (pictured), the light yellow liquid that makes up 55 per cent of our blood
Around 50 million people around the world live with Alzheimer’s disease – which accounts for between 50 per cent and 70 per cent of dementia cases.
Although the exact cause of Alzheimer’s disease is not yet fully understood, it is thought to be caused by the abnormal build-up of proteins in and around brain cells.
WHAT IS TAU?
Tau is considered a hallmark protein of Alzheimer’s disease and other brain diseases.
It’s predominantly found in brain cells (neurons). But in people with Alzheimer’s disease, the proteins are misshapen.
And Alzheimer’s disease is well known to feature tangles or clumps that are composed of tau protein.
Scientists have long pointed to the importance of tau in Alzheimer’s because of evidence linking the spread of tau with disease progression.
Another important protein is beta amyloid, the accumulation of which is largely completed at an earlier clinical stage known as mild neurocognitive disorder.
However, tau accumulation continues throughout the course of the disease, the Bright Focus Foundation reports.
Therefore, the total amount of abnormal tau in the brain is linked to disease stage and severity.
Tau clumps are not yet measurable with an available blood test, although research is ongoing.
In the case of amyloid, a PET scan won’t identify disease severity because of amyloid’s early accumulation.
Fluid from the spinal canal is taken to analyse for proteins related to dementia (known as a lumbar puncture). But this is not used routinely as a test for dementia and is more commonly used for research purposes.
One of the proteins involved is called amyloid, deposits of which form plaques around brain cells.
The other protein is called tau, deposits of which form tangles within brain cells.
Although it’s not known exactly what causes this process to begin, scientists now know that it begins many years before symptoms appear.
Led by Oskar Hansson from Lund University, the researchers developed and validated models that could predict an individual’s risk of cognitive decline and subsequent transition to Alzheimer’s disease.
They used data from 573 patients with minor cognitive impairments from two independent cohorts.
Researchers compared the accuracy of several models based on various combinations of blood biomarkers to predict cognitive decline and dementia over four years.
A decline in brain function was determined by the Mini–Mental State Examination (MMSE) – a 30-point test that consists of a series of questions and tests a number of different mental abilities, including a person’s memory, attention and language.
They found the top predictors to be P-tau181, a type of tau protein already known to be a hallmark of Alzheimer’s disease, and NfL known to be a marker of neuro-axonal damage.
Combined, they were almost 90 per cent accurate in identifying those who went on to develop the disease.
The findings demonstrate the value of using specific combinations of blood-based biomarkers to make predictions for specific individuals with MCI.
‘Like dementia, MCI is an umbrella term describing several symptoms, and can be caused by a number of different underlying diseases,’ said Dr Sara Imarisio at Alzheimer’s Research UK.
‘We know that over 50 per cent of people with MCI will go on to develop dementia, and it is important that we try to identify those who will and those who will not progress to be able to offer appropriate treatment and advice.’
However, other scientists who were not involved with the study believe further research with larger cohorts is needed.
‘This study only looked at a few hundred people, but if these blood biomarkers can predict Alzheimer’s in larger, more diverse groups, we could see a revolution in how we test new dementia drugs,’ said Dr Richard Oakley, head of research at Alzheimer’s Society.
‘Blood tests to predict dementia are moving at a break-neck speed, but if government doesn’t double dementia research funding as they promised, people with dementia won’t benefit from these new breakthroughs.’
Professor Tara Spires-Jones, a neurodegeneration expert at the University of Edinburgh, pointed out that some of the people a high predicted probability of disease based on these proteins in their blood did not go on to develop Alzheimer’s.
Likewise, some people with a low predicted probability did go on to develop the disease.
The study is an important step on the road to developing a blood test for Alzheimer’s, but it is important to note that we are not there yet,’ said Professor Spires-Jones.
‘As the authors correctly note, more studies in larger populations and standardised ways of running and interpreting these tests will be needed to confirm their usefulness.’
The study has been published in Nature Aging.
ELDERLY PEOPLE IN POLLUTED AREAS ‘MORE LIKELY TO DEVELOP ALZHEIMER’S’
Elderly people living in polluted areas are at greater risk of developing Alzheimer’s disease, warns a new study in JAMA Neurology.
Researchers looked at PET scans (positron emission tomography) from more than 18,000 elderly people in the US who had dementia or mild cognitive impairments.
They then plotted their postcodes and determined air pollution levels in each neighbourhood based on Environmental Protection Agency data, which measures ground level ozone and pollution particles in the air with a diameter less than 2.5 micrometres, known as PM2.5.
PET scans from elderly people living in the most polluted areas were 10 per cent more likely to show amyloid plaques – hard proteins which clump together between nerve cells, the researchers found.
While not all kinds of dementia are associated with these plaques, they are a hallmark of Alzheimer’s disease.
First author Dr Leonardo Iaccarino said: ‘Exposure in our daily lives to PM2.5, even at levels that would be considered normal, could contribute to induce a chronic inflammatory response.
‘Over time, this could impact brain health in a number of ways, including contributing to an accumulation of amyloid plaques.’
The more pollutants in the air, the more likely people were to have a scan with amyloid plaques, the researchers found.