Last updated February 2, 2018 at 10:00 am
Breakthrough diagnostics could be a game-changer in the treatment of Alzheimer’s.
An Australian-Japanese research team has used the protein, amyloid-β, which is already associated with Alzheimer’s disease, as a marker to develop a test that predicts people at risk of developing Alzheimer’s disease with an accuracy greater than 90 per cent.
Amyloid-ß is a protein that is currently the best marker we have that correlates with the development of Alzheimer’s disease. These proteins build up and form plaques on the brains of people with Alzheimer’s disease.
“The presence of amyloid-β in the brain is one of the first signs that something is going awry, so to be able to identify changes using a blood test, which is easy and affordable, could make a big difference to whether we can use a preventative approach in treating Alzheimer’s disease,” said Dr Estella Newcombe, an Alzheimer’s disease researcher at Queensland Brain Institute.
“It accumulates before we see any cognitive decline or other protein abnormalities.”
Taking a new approach to testing for Alzheimer’s disease
The study involved an initial discovery data set in Japan with 121 people. This method was then validated by an Australian team with 252 people. This approach alone may soon become the gold standard for developing diagnostic tests, using an independent site to validate data and strengthen the validity of the study.
Data sets included a balanced number of individuals classified as cognitively normal, individuals with mild cognitive impairment, and individuals clinically diagnosed with Alzheimer’s disease with dementia.
“Nakamura and colleagues have taken plasma samples [derived from blood] from patients with Alzheimer’s disease or mild cognitive impairment and enriched these samples for one of the proteins responsible for Alzheimer’s disease: amyloid-β. Amyloid-β results from problematic enzymatic cleavage of the amyloid precursor protein, which we all have,” summarises Dr Newcombe.
“The success of this study comes from using the amyloid precursor protein as a reference in identifying the ratio of problematic amyloid-β. By using this ratio, the researchers have reduced a significant amount of variability between individuals, leading to better reproducibility in this diagnostic tool.”
This ratio could then be used predict the level of amyloid-beta build up on a patient’s brain.
The test itself was developed by Dr Koichi Tanaka, a 2002 Nobel Prize for Chemistry winner and expert on mass spectrometry.
Improvements for Alzheimer’s disease detection
“One of the worst things about Alzheimer’s disease is that by the time you realise you have it, a lot of the damage has been done. We lack tests for Alzheimer’s disease that are cheap and reliable enough that they can be used as a pre-emptive diagnostic test; one that might mean a person is diagnosed before they suffer too much of the significant neuronal loss associated with the disease,” explains Dr Newcombe.
Currently detection methods are costly and inconvenient. In PET scans, trackable molecules are injected intravenously. They travel throutgh the blood to the brain and attach to amyloid plaques. The other method is extremely invasive, by assessing protein levels via lumbar puncture which takes the cerebrospinal fluid out from the spine.
“Nakamura and colleagues showed high reproducibility compared to PET scans, via a much easier and cheaper technique, making this plasma biomarker clinically promising. However, further international testing would be ideal, with sample collection being standardised,” said Dr Newcombe.
One of the authors of the paper, Professor Colin Masters, from the Florey Institute of Neuroscience and Mental Health, says that with earlier detection, it should lead to better outcomes for therapeutic success.
The revolutionary benefits of a biomarker diagnosis for Alzheimer’s disease
Currently, the test is only available for research-related purposes, meaning that in the more immediate future, it’s likely that this biomarker will be used for screening potential subjects for clinical trials for Alzheimer’s disease experimental treatments.
This biomarker holds a lot of potential, particularly in “screening for participants for clinical trials, particularly in the pre-clinical phases,” points out Prof Masters.
Due to the accuracy of the test, when people are cognitively normal, or have mild cognitive impairments, they will be able to know if potential subjects are on an Alzheimer’s disease pathway and thus their eligibility for a potential Alzheimer’s disease study.
Prof Masters also lists other benefits:
- Potential for population screening for public health
- Differential diagnoses – distinguishing different types of dementia in Alzheimer’s disease
- Prognostic implications – tests may contain info about how fast a person may deteriorate
- Monitoring the efficacy of any intervention, especially ones that are targeted at clearing the abnormal protein from the brain
- Future therapies – improve cost and efficacy of clinical trials for pharmaceutical companies with fast and cheaper diagnoses
This breakthrough biomarker test is a real achievement for Prof Masters, who calls it “a 30-year odyssey”. At the Florey Institute, they have been working since 1989, nearly 30 years, on the potential for a blood test for Alzheimer’s disease. Hard work has paid off, he says “we can finally say we have a high-performing blood test.”
This research was published in Nature.
Alzheimer’s disease research remains a difficult, but not impossible, task
Earlier this month, a separate research paper reported the failings of a then-promising large clinical trial in the US. The drug, solanezumab, a monoclonal antibody-based treatment for Alzheimer’s disease developed by Eli Lilly targeted amyloid plaques, but it failed to significantly slow cognitive decline.
It was the first major Alzheimer’s clinical trial to require molecular evidence of amyloid deposition in the brain for enrollment.
In commentary on this recent study, Prof Masters explained that unfortunately the drug’s “efficacy wasn’t great enough to be registered [as a success]. It showed some degree of separation between [the] treatment group and placebo group, but it wasn’t large enough.”
He says that there is still potential for this promising drug. There are plans, involving Melbourne researchers, for a future multi-centre international clinical trial with the same drug but at a higher dose and extending the length of the US study, which only ran for 18 months.
This US research was published in the New England Journal of Medicine.