New blood test measures biomarkers for detection of early Alzheimer’s disease

Alzheimer’s disease is a physical illness which damages several brain functions. The symptoms develop gradually over many years, increasing in severity over time. Accounting for 60 to 80% of all cases, Alzheimer’s disease is the most common cause of dementia. The total cost of care for people with dementia in the UK is £34.7 billion, and is expected to almost triple by 2040 unless outcomes can be improved through early identification.

There isn’t currently a test which can be used to diagnose Alzheimer’s disease, particularly in its early stages.

Preliminary results from PharmaKure, a spinout pharmaceutical company from the University of Manchester, indicate that a novel, whole blood test known as ALZmetrix™, can quantify Alzheimer’s disease biomarkers to provide early indicators of cognitive decline.

About the study

The clinical trial was blinded, so any information which may have influenced the participants or researchers was withheld until after the study’s completion. The aim of blinding a trial is to reduce experimental bias. 

Blood was taken from 54 participants, aged 50 to 80, who had had an amyloid positron emission tomography (PET) scan or cerebrospinal fluid (CSF) amyloid assessment in the last five years which gave amyloid-positive results – indicating that they were in the earliest stages of Alzheimer’s disease. The blood was shipped from the Glasgow Memory Clinic to PharmaKure in Manchester for analysis.

There are a few key biomarker proteins associated with Alzheimer’s disease. Amyloid-β (Aβ40 and Aβ42), α-synuclein and Tau (pTAU(181) and pTAU(217)). The level of these biomarker proteins present in blood were measured to determine whether patients had amyloid deposits in their brain, and to predict how far they had progressed towards full Alzheimer’s disease, compared to PET scans and CSF findings.

Machine learning tools combined the blood biomarker and patient data (age, gender, amyloid status, and presence or absence of the ApoE4 gene – the most prevalent genetic risk factor for Alzheimer’s disease) in an optimal way to develop predictors.

Findings from clinical trials

The study’s results confirm that analysing the whole blood sample, rather than only the blood plasma fraction, can identify people who are at high risk of developing full Alzheimer’s disease. The machine learning software also indicates which biomarkers are most useful for this purpose.

Plasma is the clear, liquid component of blood which does not contain blood cells. It is typically used by researchers to detect disease-related proteins. However, oligomers – small toxic molecules – are located on blood cells, but hardly any are found in plasma. Blood is traditionally very difficult to use in tests for Alzheimer’s disease due to its high viscosity, or thickness. PharmaKure’s biomarker technology claims to overcome the physical problems associated with screening whole blood.

Professor Andrew Doig, Head of R&D at PharmaKure and a researcher at The University of Manchester, said, “We are particularly pleased to find that our ALZmetrix™ blood test can differentiate between patient groups that are amyloid positive or amyloid negative with 97% accuracy to predict those at highest risk of Alzheimer’s Disease.”

Skewed by unrepresentative data

Current cut-off points for biomarkers used to determine Alzheimer’s disease status were developed using predominantly Caucasian patients, which raises concern about the validity of these tests for other racial demographics. For instance, some studies report lower cerebrospinal fluid (CSF) levels of Tau biomarkers in Black/African-American individuals compared to Caucasian individuals. Additionally, studies on American Indian patients show no evidence of neurodegenerative risk from ApoE4.

It is therefore important to ensure better representation of racially minoritised groups in Alzheimer’s research, so tests that perform equally well in all individuals can be identified and prioritised to reduce disparities in clinical outcomes.

PharmaKure will carry out a larger study where an independent laboratory will validate the results, before clearance to roll out the test is granted.

Dr Farid Khan, CEO at PharmaKure Limited, said, “We will be using the exciting data to expand our ALZmetrix™ test to additional patients and new biomarkers.”

Testing for Alzheimer’s disease looking forward

Using whole blood may enable the development of a screening system to identify Alzheimer’s disease early on, before any major cognitive decline becomes apparent. This would allow treatments to be offered sooner, improving health outcomes for populations, lowering costs to our health system, and improving the quality of life of millions.

Dr Bob Smith, Clinical Director at PharmaKure, said, “Using the ALZmetrix™ test for Alzheimer’s could provide a low cost, easily accessible test […] as an alternative to expensive brain scans or other plasma-based tests.”

If you’re interested in learning more about this study, keep an eye out as the results are likely to be published in a journal in the next few months.